Short-Term Exposure to Foodborne Xenoestrogens Affects Breast Cancer Cell Morphology and Motility Relevant for Metastatic Behavior In Vitro.

Breast cancer is highly susceptible to metastasis formation. During the time of disease progression, tumor pathophysiology can be impacted by endogenous factors, like hormonal status, as well as by environmental exposures, such as those related to diet and lifestyle. New lines of evidence point toward a potential role for foodborne endocrine disruptive chemicals in this respect; however, mechanistic understanding remains limited. At the molecular level, crucial steps toward metastasis formation include cell structural changes, alteration of adhesion, and reorganization of cytoskeletal proteins involved in motility. Hence, this study investigates the potential of dietary xenoestrogens to impact selected aspects of breast cancer cell mechanotransduction. Taking the onset of the metastatic cascade as a model, experiments focused on cell-matrix adhesion, single-cell migration, and adaptation of cell morphology. Dietary mycoestrogens alternariol (AOH, 1 µM) and α-zearalenol (α-ZEL, 10 nM), soy isoflavone genistein (GEN, 1 µM), and food packaging plasticizer bisphenol A (BPA, 10 nM) were applied as single compounds or in mixtures. Pursuing the hypothesis that endocrine active molecules could affect cell functions beyond the estrogen receptor-dependent cascade, experiments were performed comparing the MCF-7 cell line to the triple negative breast cancer cells MDA MB-231. Indeed, the four compounds functionally affected the motility and the adhesion of both cell types. These responses were coherent with rearrangements of the actin cytoskeleton and with the modulation of the expression of integrin ß1 and cathepsin D. Mechanistically, molecular dynamics simulations confirmed a potential interaction with fragments of the α1 and ß1 integrin subunits. In sum, dietary xenoestrogens proved effective in modifying the motility and adhesion of breast cancer cells, as predictive end points for metastatic behavior in vitro. These effects were measurable after short incubation times (1 or 8 h) and contribute to shed novel light on the activity of compounds with hormonal mimicry potential in breast cancer progression.

Predictors of damage accrual and its impact on health-related quality of life of thrombotic antiphospholipid syndrome: Independent validation of the damage index for antiphospholipid syndrome (DIAPS).

OBJECTIVES: We aim to independently assess the validity of the damage index for antiphospholipid syndrome (DIAPS) in thrombotic antiphospholipid syndrome (APS) patients by exploring the prevalence and risk factors of organ damage and evaluating its impact on health-related quality of life (HR-QoL). METHODS: Cross-sectional study including all thrombotic APS patients (Sydney criteria) attending a Portuguese tertiary centre. Damage was assessed using the DIAPS, and HR-QoL using the 3- and 5-level EuroQol HR-QoL (EQ-D5-3L and 5L), and Visual Analogue Scale (VAS) applied via a phone questionnaire. Spearman's correlation between DIAPS and the HR-QoL scales was performed. Risk factors for damage accrual and HR-QoL impairment were explored using univariate and multivariate logistic regression. RESULTS: Among the 108 patients (female, 65.7%; white, 90.7%; primary APS, 75.9%; median disease duration, 6 years), damage (DIAPS≥1) developed in 48.2% of patients (mean ± SD DIAPS, 3.08 ± 1.83). DIAPS's neuropsychiatric domain was the most affected (24.2%), followed by the peripheral vascular domain (20.3%). No clinical, demographic nor laboratory parameters were significantly associated with damage. Regarding HR-QoL, pain/discomfort, anxiety/depression and usual activities domains were the most frequently impaired in both scales. DIAPS's domains correlated similarly with the EQ-5D-3L and 5L scales' individual domains. Female sex, medical disorders, secondary APS and type of presenting thrombosis (arterial) increased the risk of HR-QoL impairment. Total DIAPS was associated with higher odds of mobility, self-care and pain/discomfort impairment in both EQ-5D-3L and 5L scales but lost its independent risk in multivariable analysis. CONCLUSION: This external validation of DIAPS reinforces the ability of the score to correlate with HR-QoL while also highlighting risk factors for HR-QoL impairment other than damage accrual.

Multimodal influences on learning walks in desert ants (Cataglyphis fortis).

Ants are excellent navigators using multimodal information for navigation. To accurately localise the nest at the end of a foraging journey, visual cues, wind direction and also olfactory cues need to be learnt. Learning walks are performed at the start of an ant's foraging career or when the appearance of the nest surrounding has changed. We investigated here whether the structure of such learning walks in the desert ant Cataglyphis fortis takes into account wind direction in conjunction with the learning of new visual information. Ants learnt to travel back and forth between their nest and a feeder, and we then introduced a black cylinder near their nest to induce learning walks in regular foragers. By doing this across days with different wind directions, we were able to probe how ants balance different sensory modalities. We found that (1) the ants' outwards headings are influenced by the wind direction with their routes deflected such that they will arrive downwind of their target, (2) a novel object along the route induces learning walks in experienced ants and (3) the structure of learning walks is shaped by the wind direction rather than the position of the visual cue.

In Vitro Antimicrobial Activity of Isopimarane-Type Diterpenoids.

The antimicrobial evaluation of twelve natural and hemisynthetic isopimarane diterpenes are reported. The compounds were evaluated against a panel of Gram-positive bacteria, including two methicillin-resistant Staphylococcus aureus (MRSA) strains and one vancomycin-resistant Enterococcus (VRE) strain. Only natural compounds 7,15-isopimaradien-19-ol (1) and 19-acetoxy-7,15-isopimaradien-3ß-ol (6) showed promising results. Isopimarane (1) was the most active, showing MIC values between 6.76 µM against S. aureus (ATCC 43866) and 216.62 µM against E. faecalis (FFHB 427483) and E. flavescens (ATCC 49996). Compound (6) showed moderated activity against all tested microorganisms (MIC between value 22.54 and 45.07 µM). These compounds were found to be active against the methicillin-sensitive strains of S. aureus (CIP 106760 and FFHB 29593), showing MIC values of 13.55 (1) and 22.54 (6) µM. Both compounds were also active against vancomycin-resistant E. faecalis (ATCC 51299) (MIC values of 54.14 and 45.07 µM, respectively). In addition, the cytotoxicity of nine compounds 7,15-isopimaradien-3ß,19-diol (2); mixture: 15-isopimarene-8ß-isobutyryloxy-19-ol and 15-isopimarene-8ß-butyryloxy-19-ol (3); 3ß-acetoxy-7,15-isopimaradiene-19-ol (5); 19-acetoxy-7,15-isopimaradiene-3ß-ol (6); 3ß,19-diacetoxy-7,15-isopimaradiene (8); 15-isopimarene-8ß,19-diol (9); 19-O-ß-d-glucopyranoside-7,15-isopimaradiene (10); lagascatriol-16-O-ß-d-glucopyranoside (11) and lagascatriol-16-O-α-d-mannopyranoside (12) was evaluated in the human breast cancer cell line MDA-MB-231. Isopimarane (2) was the only compound showing some cytotoxicity. The IC50 value of compound (2) was 15 µM, suggesting a mild antiproliferative activity against these breast cancer cells.

Choline- versus imidazole-based ionic liquids as functional ingredients in topical delivery systems: cytotoxicity, solubility, and skin permeation studies.

BACKGROUND: Poor drug solubility represents a problem for the development of topical formulations. Since ionic liquids (ILs) can be placed in either lipophilic or hydrophilic solutions, they may be advantageous vehicles in such delivery systems. Nonetheless, it is vital to determine their usefulness when used at concentrations were cell viability is maintained, which was considered herein. METHOD: Five different ILs were prepared-three imidazole-based ILs: [C2mim][Br], [C4mim][Br], and [C6mim][Br]; and two choline-based ILs: [Cho][Phe] and [Cho][Glu]. Their cytotoxicity in human keratinocytes (HaCat cells), their influence in drug solubility and in percutaneous permeation, using pig skin membranes, was evaluated. RESULTS: Caffeine and salicylic acid were used as model actives. Choline-based ILs proved to be more suitable as functional ingredients, since they showed higher impact on drug solubility and a lower cytotoxicity. The major solubility enhancement was observed for caffeine and further solubility studies were carried out with this active in several concentrations of the choline-based ILs (0.1; 0.2; 0.5; 1.0; 3.0 and 5.0%, w/w) at 25 °C and 32 °C. Solubility was greatly influenced by concentrations up to 0.5%. The choline-based ILs showed no significant impact on the skin permeation, for both actives. The size of the imidazole-based ILs alkyl chain enhances the caffeine solubility and permeation, but also the ILs cytotoxicity. Stable O/W emulsions and gels were prepared containing the less toxic choline-based ILs and caffeine. CONCLUSIONS: Our results indicate that the choline-based ILs were effective functional ingredients, since, when used at nontoxic concentrations, they allowed a higher drug loading, while maintaining the stability of the formulations.

Unsaponifiable matter from oil of green coffee beans: cosmetic properties and safety evaluation.

CONTEXT: Unsaponifiable matter (UM), a fraction of green coffee oil (GCO) contains functional compounds responsible for desirable cosmetic properties such as UV-B absorption. OBJECTIVES: To evaluate oil content and sun protection factor (SPF) variability of the two most important species of coffee and, the toxic and cytotoxic effects, as well as cosmetic properties, including antioxidant and antimicrobial activities of UM obtained from green Coffea arabica seed oil. MATERIALS AND METHODS: The safety and potential cosmetic properties of UM extracted from green coffee oil (GCO) were evaluated by the brine shrimp viability and the MTT cytotoxicity assays. The SPF and antioxidant activity were evaluated using in vitro methods. RESULTS: Relevant cytotoxicity was found against keratinocytes for concentrations ≥25 µg/mL and in the brine shrimp assay (LC50 24 µg/mL). Antimicrobial and antioxidant activities (IC50 1448 µg/mL) were low in UM but SPF was 10 times higher than in GCO. CONCLUSION: UM is a novel potential UV-B absorbent but its use as a cosmetic ingredient should be better considered due to the considerable cytotoxicity shown in the experimental conditions described.

Genetic Variation of MT-ND Genes in Frontotemporal Lobar Degeneration: Biochemical Phenotype-Genotype Correlation.

BACKGROUND: Frontotemporal lobar degeneration (FTLD) is the second most common early-onset dementia. Over the last few decades, a growing number of evidence suggests mitochondrial involvement in neurodegeneration, namely modifications of mitochondrial DNA (mtDNA) contributing to energy impairment. OBJECTIVE: To sequence the 7 mitochondrially encoded complex I (MT-ND) genes in 70 FTLD patients and investigate mitochondrial respiratory chain (MRC) complex I activity. METHODS: A sample of 70 patients was studied (39 females and 31 males; age range: 38-82 years, mean ± SD: 63 ± 11 years) with a probable diagnosis of FTLD. Total DNA was extracted from peripheral blood, and sequencing analysis of 7 MT-NDn (1, 2, 3, 4L, 4, 5, 6) genes was performed. Variants identified were submitted to in silico study. Spectrophotometric evaluation of MRC activity in lymphocytes was performed, and results were compared with age-matched controls. RESULTS: A total of 358 (161 different) alterations were found in 92.9% of patients. According to in silico analysis of nonsynonymous variants, only 5 variations are possibly or probably damaging. Complex I activity is significantly decreased in patients. CONCLUSION: To our knowledge, this is the first report of the complete sequence of the MT-ND genes in FTLD patients and correlation with MRC activity. The high number of mtDNA variations identified and a significant decrease in complex I activity suggest a possible involvement of mtDNA alterations in FTLD. Although the majority of these alterations are not primarily pathogenic, an interaction with other mutations may occur, leading to the disease, worsening its expression or influencing age of onset.

Personal care products in soil-plant and hydroponic systems: Uptake, translocation, and accumulation.

Personal care products (PCPs) are organic compounds that are incorporated in several daily life products, such as shampoos, lotions, perfumes, cleaning products, air fresheners, etc. Due to their massive and continuous use and because they are not routinely monitored in the environment, these compounds are considered emerging contaminants. In fact, residues of PCPs are being discharged into the sewage system, reaching wastewater treatment plants (WWTPs), where most of these compounds are not completely degraded, being partially released into the environment via the final effluents and/or accumulating in the sewage sludges. Environmental sustainability is nowadays one of the main pillars of society and the application of circular economy models, promoting the waste valorisation, is increasingly encouraged. Therefore, irrigation with reclaimed wastewater or soil fertilization with sewage sludge/biosolids are interesting solutions. However, these practices raise concerns due to the potential risks associated to the presence of hazardous compounds, including PCPs. When applied to agricultural soils, PCPs present in these matrices can contaminate the soil or be taken up by crops. Crops can therefore become a route of exposure for humans and pose a risk to public health. However, the extent to which PCPs are taken up and bioaccumulated in crops is highly dependent on the physicochemical properties of the compounds, environmental variables, and the plant species. This issue has attracted the attention of scientists in recent years and the number of publications on this topic has rapidly increased, but a systematic review of these studies is lacking. Therefore, the present paper reviews the uptake, accumulation, and translocation of different classes of PCPs (biocides, parabens, synthetic musks, phthalates, UV-filters) following application of sewage sludge or reclaimed water under field and greenhouse conditions, but also in hydroponic systems. The factors influencing the uptake mechanism in plants were also discussed.

Evidence of Browning and Inflammation Features in Visceral Adipose Tissue of Women with Endometriosis.

BACKGROUND: Patients with endometriosis tend to have a low body mass index, suggesting an inverse relationship between body fat and risk of disease. This is supported by evidence that miRNAs differentially expressed in endometriosis induce browning of pre-adipocytes in vitro. Thus, we hypothesize that endometriosis may underlie adipose tissue (AT) dysfunction and browning. AIMS: Identify inflammation and browning processes in AT collected from endometriosis patients. METHODS: Visceral and subcutaneous AT samples were obtained during endometriosis (n = 32) or uterine myoma (n = 14; controls) surgery. Blood catecholamines were determined by high-performance liquid chromatography while IL-6 and TGF-ß levels were quantified by ELISA. Adipocyte cross-sectional areas were analyzed in H&E-stained sections by computer-assisted morphometry. Macrophages (F4/80; Galectin-3) and browning activation (UCP-1; PGC-1α) in tissues were identified by dual label immunofluorescence. Expression of inflammatory (IL-6; MCP-1; Galectin-3; CD206; TIMP1; TGF-ß) and browning-related (UCP-1; PGC-1α; DIO2; CITED1; CIDEA; TMEM26; TBX1; PRDM16; PPAR-γ) molecules in AT were assessed by RT-PCR and Western blotting. RESULTS: Compared to controls, patients presented smaller adipocytes, especially in VAT, and lower norepinephrine levels. Serum IL-6, but not TGF-ß, was increased in patients. UCP-1, PGC-1α, IL-6, and MCP-1 were upregulated in VAT from endometriosis women, which also evidenced a reduction of CD206, relative to controls. However, no differences were found in mRNA expression of IL-6, TIMP1, and TGF-ß nor Galectin-3 protein levels. In SAT, protein expression remained unchanged between patients and controls. CONCLUSIONS: Our findings support an endometriosis' role as a pro-catabolic state along with local signals of VAT browning and inflammation.

Antitumoral Activity of Cecropia Pachystachya Leaves Extract in Vitro and in Vivo Model of Rat Glioma: Brain and Blood Effects.

The aim of this study was to investigate the antiglioma effect of Cecropia pachystachya Trécul (CEC) leaves extract against C6 and U87 glioblastoma (GB) cells and in a rat preclinical GB model. The CEC extract reduced in vitro cell viability and biomass. In vivo, the extract decreased the tumor volume approximately 62%, without inducing systemic toxicity. The deficit in locomotion and memory and an anxiolytic-like behaviors induced in the GB model were minimized by CEC. The extract decreased the levels of reactive oxygen species, nitrites and thiobarbituric acid reactive substances and increased the activity of antioxidant enzymes in platelets, sera and brains of GB animals. The activity of NTPDases, 5'-nucleotidase and adenosine deaminase (ADA) was evaluated in lymphocytes, platelets and serum. In platelets, ATP and AMP hydrolysis was reduced and hydrolysis of ADP and the activity of ADA were increased in the control, while in CEC-treated animals no alteration in the hydrolysis of ADP was detected. In serum, the reduction in ATP hydrolysis was reversed by CEC. In lymphocytes, the increase in the hydrolysis of ATP, ADP and in the activity of ADA observed in GB model was altered by CEC administration. The observed increase in IL-6 and decrease in IL-10 levels in the serum of GB animals was reversed by CEC. These results demonstrate that CEC extract is a potential complementary treatment to GB, decreasing the tumor size, while modulating aspects of redox and purinergic systems.

Insectivorous bat activity dataset across different land-use types in the Islands of São Tomé and Príncipe, Central West Africa.

Background: São Tomé and Príncipe oceanic islands, in Central West Africa, are characterised by exceptional levels of endemism. Since human colonisation in the mid-15th century, São Tomé and Príncipe have lost 74% and 67% of their native habitat, respectively. Today, these islands are mainly covered by remaining old-growth forests, secondary regrowth forests, shaded plantations (mostly of cocoa), oil palm plantations (in the case of São Tomé), small-scale agricultural areas and urban areas. Yet, little is known about how species on these islands are coping with land-use changes. Island ecosystems are particularly important for bats, with about 25% of the world's bat species being entirely restricted to island systems. São Tomé and Príncipe Islands comprise six and four native insectivorous bats, respectively. Two species, Chaerephontomensis and Macronycteristhomensis, are island-endemics in São Tomé; Pseudoromiciaprincipis is an island-endemic in Príncipe; and Miniopterusnewtoni is endemic from both São Tomé and Príncipe. Here, we present a dataset comprising a comprehensive compilation of occurrence records derived from acoustic sampling of insectivorous bats across the predominant land-use types of both the São Tomé and Príncipe Islands. In each sampling site, standardised surveys consisted of deploying one Audio Moth device that recorded for 1 minute every 5 minutes over a 48-hour period. We identified a total of 19,437 bat-passes across the 115 sites surveyed in São Tomé Island and 17,837 bat-passes across the 50 sites surveyed in Príncipe Island. New information: Based on a sampling effort of 1,584 hours of recordings manually processed to identify all the contained bat passes, this dataset, publicly available on GBIF, provides comprehensive information on the activity of insectivorous bats across two endemic-rich oceanic islands in the Gulf of Guinea. For each bat pass identified, we report the identified species, geographic coordinates, land-use type, altitude, date and time. This is the first public dataset providing detailed information on species-level habitat use for insectivorous bats on oceanic islands in Africa.

Differential effects of methoxyamine on doxorubicin cytotoxicity and genotoxicity in MDA-MB-231 human breast cancer cells.

Pharmacological inhibition of DNA repair is a promising approach to increase the effectiveness of anticancer drugs. The chemotherapeutic drug doxorubicin (Dox) may act, in part, by causing oxidative DNA damage. The base excision repair (BER) pathway effects the repair of many DNA lesions induced by reactive oxygen species (ROS). Methoxyamine (MX) is an indirect inhibitor of apurinic/apyrimidinic endonuclease 1 (APE1), a multifunctional BER protein. We have evaluated the effects of MX on the cytotoxicity and genotoxicity of Dox in MDA-MB-231 metastatic breast cancer cells. MX has little effects on the viability and proliferation of Dox-treated cells. However, as assessed by the cytokinesis-block micronucleus assay (CBMN), MX caused a significant 1.4-fold increase (P<0.05) in the frequency of micronucleated binucleated cells induced by Dox, and also altered the distribution of the numbers of micronuclei. The fluorescence probe dihydroethidium (DHE) indicated little production of ROS by Dox. Overall, our results suggest differential outcomes for the inhibition of APE1 activity in breast cancer cells exposed to Dox, with a sensitizing effect observed for genotoxicity but not for cytotoxicity.

Induction of sister chromatid exchange by acrylamide and glycidamide in human lymphocytes: role of polymorphisms in detoxification and DNA-repair genes in the genotoxicity of glycidamide.

Acrylamide (AA) is a probable human carcinogen generated in carbohydrate-rich foodstuffs upon heating. Glycidamide (GA), formed via epoxidation, presumably mediated by cytochrome P450 2E1, is considered to be the active metabolite that plays a central role in the genotoxicity of AA. The aim of this work was to evaluate the cytogenetic damage induced by AA and GA in cultured human lymphocytes by use of the sister chromatid exchange (SCE) assay. Furthermore, this report addresses the role of individual genetic polymorphisms in key genes involved in detoxification and DNA-repair pathways (BER, NER, HRR and NHEJ) on the induction of SCE by GA. While AA induced the number of SCE/metaphase only slightly, especially for the highest concentration tested (2000µM), GA markedly induced SCEs in a concentration-dependent manner up to concentrations of 750µM, leading to an increase in SCEs of up to about 10-fold compared with controls. By combining DNA damage in GA-treated lymphocytes and data on polymorphisms, associations between the induction of SCEs with GSTP1 (Ile105Val) and GSTA2 (Glu210Ala) genotypes are suggested.

Consumers' practices and safety perceptions regarding the use of materials for food preparation and storage: Analyses by age group.

Food Contact Materials (FCM) are those intended to be in contact with food, during its production, handling, and storage. FCM contain chemicals that could migrate to the foodstuff, posing potential health concerns, and usage practices influence the level of migration. This study assesses the preferences, safety perceptions, and usage practices of Portuguese consumers regarding FCM used for cooking and food storage (cookware). An observational, quantitative, and transversal study was performed through an online survey created for this purpose, which involved 1179 Portuguese adults. Results were analyzed according to age. Safety was the factor considered most important when choosing cookware materials, although the choice criteria varied with age. The majority of respondents recognize the risk of food contamination through cookware. Stainless steel and glass were considered the safest materials for cooking. The materials most used to reserve food are glass and plastic. Older individuals carry out more maintenance of cookware and have greater knowledge about how to wash and store it. Regarding the FCM symbology, there is a general lack of knowledge. Our study demonstrates the need to disseminate reliable information to the general public about cookware, contributing to greater literacy in health and to less exposure to food contact chemicals.

The Golgi Apparatus as an Anticancer Therapeutic Target.

Although the discovery of the Golgi apparatus (GA) was made over 125 years ago, only a very limited number of therapeutic approaches have been developed to target this complex organelle. The GA serves as a modification and transport center for proteins and lipids and also has more recently emerged as an important store for some ions. The dysregulation of GA functions is implicated in many cellular processes associated with cancer and some GA proteins are indeed described as cancer biomarkers. This dysregulation can affect protein modification, localization, and secretion, but also cellular metabolism, redox status, extracellular pH, and the extracellular matrix structure. Consequently, it can directly or indirectly affect cancer progression. For these reasons, the GA is an appealing anticancer pharmacological target. Despite this, no anticancer drug specifically targeting the GA has reached the clinic and few have entered the clinical trial stage. Advances in nanodelivery approaches may help change this scenario by specifically targeting tumor cells and/or the GA through passive, active, or physical strategies. This article aims to examine the currently available anticancer GA-targeted drugs and the nanodelivery strategies explored for their administration. The potential benefits and challenges of modulating and specifically targeting the GA function in the context of cancer therapy are discussed.

Predictive Factors of Tolerance in Office Hysteroscopy - a 3-Year Analysis from a Tertiary Center.

OBJECTIVE: Pain is the primary limitation to performing hysteroscopy. We aimed to evaluate the predictive factors of low tolerance to office hysteroscopic procedures. METHODS: Retrospective cohort study of the patients who underwent office hysteroscopy from January 2018 to December 2020 at a tertiary care center. Pain tolerance to office-based hysteroscopy was subjectively assessed by the operator as terrible, poor, moderate, good, or excellent. Categorical variables were compared with the use of the Chi-squared test; an independent-samples t-test was conducted to compare continuous variables. Logistic regression was performed to determine the main factors associated with low procedure tolerance. RESULTS: A total of 1,418 office hysteroscopies were performed. The mean age of the patients was 53 ± 13.8 years; 50.8% of women were menopausal, 17.8% were nulliparous, and 68.7% had a previous vaginal delivery. A total of 42.6% of women were submitted to an operative hysteroscopy. Tolerance was categorized as terrible or poor in 14.9% of hysteroscopies and moderate, good, or excellent in 85.1%. A terrible or poor tolerance was more frequently reported in menopausal women (18.1% vs. 11.7% in premenopausal women, p = 0.001) and women with no previous vaginal delivery (18.8% vs. 12.9% in women with at least one vaginal birth, p = 0.007). Low tolerance led more often to scheduling a second hysteroscopic procedure under anesthesia (56.4% vs. 17.5% in reasonable-to-excellent tolerance, p < 0.0005). CONCLUSION: Office hysteroscopy was a well-tolerated procedure in our experience, but menopause and lack of previous vaginal delivery were associated with low tolerance. These patients are more likely to benefit from pain relief measures during office hysteroscopy.

Genetic polymorphisms in detoxification and DNA repair genes and susceptibility to glycidamide-induced DNA damage.

Acrylamide (AA) is a probable human carcinogen formed in carbohydrate-rich foodstuffs upon heating. Glycidamide (GA), the AA metabolite formed by epoxidation, is considered the ultimate genotoxic agent. In this study, the in vitro genotoxic potential of AA and GA in human whole blood leukocytes was compared using the alkaline comet assay. Although AA did not induce significant DNA damage in the concentrations tested (up to 1000 µM), GA markedly increased the percentage of tail DNA at concentrations ≥250 µM. Further, this study addressed the role of genetic polymorphisms in key genes involved in metabolism and DNA repair pathways (BER, NER, HRR, and NHEJ) on GA-induced genotoxicity assessed by the alkaline comet assay. The results obtained suggested associations between DNA damage and polymorphisms of BER (MUTYH Gln335His and XRCC1 Gln399Arg) and NER (XPC Ala499Val) genes, either alone or in combination.

Redox-Active Molecules as Therapeutic Agents.

Oxidative stress and altered redox signaling have been described in a plethora of pathological conditions, such as inflammation, cardiovascular diseases, diabetes, cancer, and neurodegenerative disorders, among others [...].

GOLGI: Cancer cell fate control.

Growing evidence connects many of the Golgi known functions with cellular events related to cancer initiation and progression, including regulation of cell survival/death, proliferation, motility, metabolism and immune evasion. However, a broad and integrated understanding of the impact of the Golgi on cancer cell phenotype has not yet been achieved. Multiple cellular events involving the Golgi are associated with protein and lipid modification and trafficking. However, less explored aspects of this enigmatic organelle also contribute to cell fate decision-making by impacting signal transduction, redox and ion homeostasis. This article focuses on the molecular mechanisms and Golgi proteins underlying the impact of the Golgi on cancer cell phenotype. Special emphasis is given to emerging knowledge on redox and ion homeostasis. Current and potential cancer progression therapeutic strategies associated with this organelle will also be addressed.

Uptake and translocation of synthetic musk fragrances by pea plant grown in sewage sludge-amended soils.

Sewage sludges are rich in organic matter and several essential nutrients for plant growth, making them very appealing for application in agricultural soils. However, they may also contain a wide range of emerging pollutants, which has raised concerns about the potential risks of this practice to crops, the environment, and public health - accumulation in soils and/or plant uptake and translocation of contaminants. Therefore, there is a need to study plant-soil interactions and assess the uptake potential of these contaminants by food crops to better understand these risks. The main aim of this work was to assess the possible drawbacks of sludge application to cropland, by observing the impact on the growth and yield of a model crop (pea plant - Pisum sativum) grown over an 86-day greenhouse experiment and by assessing the uptake potential of synthetic musk fragrances. Different sewage sludge application rates (4-30-ton ha-1) and initial concentrations of contaminants were tested. The application of sludge yielded benefits to the cultivated plants, finding improved crop productivity with an application rate of 30-ton ha-1. At the end of the experiment, soil samples and plants separated into sections were analysed using a QuEChERS extraction methodology followed by gas chromatography-mass spectrometry (GC-MS) quantification. Galaxolide (HHCB) and tonalide (AHTN) underwent uptake by the plant roots, having been detected in concentrations up to 346 ng g-1 on a dry weight basis (dw), but only HHCB was detected in above ground tissues. At the end, a decrease in the levels of synthetic musks in the amended soils (>80% in several instances) was observed. Assuming the worst-case scenario, no risk to human health was observed from the ingestion of peas grown on sewage sludge-amended soils. However, a soil hazard quotient analysis yielded worryingly high quotient values for AHTN in nearly all tested conditions.