Periodontitis exacerbation during pregnancy in mice: Role of macrophage migration inhibitory factor as a key inductor.

OBJECTIVE: The present study was designed to investigate the role of macrophage migration inhibitory factor (MIF) in the exacerbation of pregestational periodontal disease (PGPD). BACKGROUND: Periodontitis (PT) is a severe stage of periodontal disease characterized by inflammation of the supporting tissues of the teeth, which usually worsens during pregnancy. MIF is a proinflammatory cytokine that is significantly elevated in periodontitis, both at the beginning and at the end of pregnancy. Although periodontitis usually presents with greater severity during pregnancy, the participation of MIF in the evolution of periodontitis has not been established. METHODS: To analyze the relevance of MIF in the exacerbation of PGPD, we employed a model of PGPD in WT and Mif-/- mice, both with a BALB/c genetic background. PT was induced with nylon suture ligatures placed supramarginally around the second upper right molar. For PGPD, PT was induced 2 weeks before mating. We evaluated histological changes and performed histometric analysis of the clinical attachment loss, relative expression of MMP-2 and MMP-13 by immunofluorescence, and relative expression of the cytokines mif, tnf-α, ifn-γ, and il-17 by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Our data revealed that periodontal tissue from PGPD WT mice produced a twofold increase in MIF compared with PT WT mice. Moreover, the evolution of periodontitis in Mif-/- mice was less severe than in PGDP WT mice. Periodontal tissue from Mif-/- mice with PGPD produced 80% less TNF-α and no IFN-γ, as well as 50% lower expression of matrix metalloproteinase (MMP)-2 and 25% less MMP-13 compared to WT PGDP mice. CONCLUSIONS: Our study suggests that MIF plays an important role in the exacerbation of periodontitis during pregnancy and that MIF is partially responsible for the inflammation associated with the severity of periodontitis during pregnancy.

Activity of propolis from Mexico on the proliferation and virulence factors of Candida albicans.

BACKGROUND: This research evaluated the anti-Candida albicans effect of Mexican propolis from Chihuahua. Chemical composition of the ethanolic extract of propolis was determined by GC-MS, HPLC-DAD, and HPLC-MS. The presence of anthraquinone, aromatic acid, fatty acids, flavonoids, and carbohydrates was revealed. RESULTS: The anti-Candida activity of propolis was determined. The inhibitions halos were between 10.0 to 11.8 mm; 25% minimum inhibitory concentration (0.5 mg/ml) was fungistatic, and 50% minimum inhibitory concentration (1.0 mg/ml) was fungicidal. The effect of propolis on the capability of C. albicans to change its morphology was evaluated. 25% minimum inhibitory concentration inhibited to 50% of germ tube formation. Staining with calcofluor-white and propidium iodide was performed, showing that the propolis affected the integrity of the cell membrane. INT1 gene expression was evaluated by qRT-PCR. Propolis significantly inhibited the expression of the INT1 gene encodes an adhesin (Int1p). Chihuahua propolis extract inhibited the proliferation of Candida albicans, the development of the germ tube, and the synthesis of adhesin INT1. CONCLUSIONS: Given the properties demonstrated for Chihuahua propolis, we propose that it is a candidate to be considered as an ideal antifungal agent to help treat this infection since it would not have the toxic effects of conventional antifungals.

Airborne particulate matter (PM10) induces cell invasion through Aryl Hydrocarbon Receptor and Activator Protein 1 (AP-1) pathway deregulation in A549 lung epithelial cells.

BACKGROUND: Particulate matter with an aerodynamic size ≤ 10 µm (PM10) is a risk factor for lung cancer development, mainly because some components are highly toxic. Polycyclic aromatic hydrocarbons (PAHs) are present in PM10, such as benzo[a]pyrene (BaP), which is a well-known genotoxic and carcinogenic compound to humans, capable of activating AP-1 transcription factor family genes through the Aryl Hydrocarbon Receptor (AhR). Because effects of BaP include metalloprotease 9 (MMP-9) activation, cell invasion, and other pathways related to carcinogenesis, we aimed to demonstrate that PM10 (10 µg/cm2) exposure induces the activation of AP-1 family members as well as cell invasion in lung epithelial cells, through AhR pathway. METHODS AND RESULTS: The role of the AhR gene in cells exposed to PM10 (10 µg/cm2) and BaP (1µM) for 48 h was evaluated using AhR-targeted interference siRNA. Then, the AP-1 family members (c-Jun, Jun B, Jun D, Fos B, C-Fos, and Fra-1), the levels/activity of MMP-9, and cell invasion were analyzed. We found that PM10 increased AhR levels and promoted its nuclear localization in A549 treated cells. Also, PM10 and BaP deregulated the activity of AP-1 family members. Moreover, PM10 upregulated the secretion and activity of MMP-9 through AhR, while BaP had no effect. Finally, we found that cell invasion in A549 cells exposed to PM10 and BaP is modulated by AhR. CONCLUSION: Our results demonstrated that PM10 exposure induces upregulation of the c-Jun, Jun B, and Fra-1 activity, the expression/activity of MMP-9, and the cell invasion in lung epithelial cells, effects mediated through the AhR. Also, the Fos B and C-Fos activity were downregulated. In addition, the effects induced by PM10 exposure were like those induced by BaP, which highlights the potentially toxic effects of the PM10 mixture in lung epithelial cells.

Curcumin-loaded microemulsion: formulation, characterization, and in vitro skin penetration.

OBJECTIVE: Formulation of curcumin in a microemulsion with a high loading capacity and that favors its penetration into the skin. SIGNIFICANCE: Take advantage of the properties of microemulsions to promote the penetration of curcumin into the skin, with the aim of enhancing its therapeutic effects. METHODS: Curcumin was formulated in microemulsions based on oleic acid (oil phase), Tween® 80 (surfactant), and Transcutol® HP (cosurfactant). The microemulsion formation area was mapped by constructing pseudo-ternary diagrams for surfactant:co-surfactant ratios 1:1, 1:2, and 2:1. Microemulsions were characterized through measurements of specific weight, refractive index, conductivity, viscosity, droplet size, and in vitro skin permeation studies. RESULTS: Nine microemulsions were prepared and characterized, showing clear, stable formulations with globule size dependent on the proportion of the components. The microemulsion with the highest loading capacity (60 mg/mL), based on Tween® 80, Transcutol® HP, oleic acid, and water (40:40:10:10) was able to penetrate the viable epidermis, finding a total amount of curcumin in the receptor medium at 24 h of 10.17 ± 9.7 µg/cm2. The distribution of curcumin in the skin, visualized by confocal laser scanning microscopy, showed that the maximum amount was located between 20 and 30 µm. CONCLUSION: The inclusion of curcumin in a microemulsion allows its passage into and through the skin. The localization of curcumin, especially in the viable epidermis, would be important for those cases where local conditions are sought to be treated.

The Road to Malignant Cell Transformation after Particulate Matter Exposure: From Oxidative Stress to Genotoxicity.

In cells, oxidative stress is an imbalance between the production/accumulation of oxidants and the ability of the antioxidant system to detoxify these reactive products. Reactive oxygen species (ROS), cause multiple cellular damages through their interaction with biomolecules such as lipids, proteins, and DNA. Genotoxic damage caused by oxidative stress has become relevant since it can lead to mutation and play a central role in malignant transformation. The evidence describes chronic oxidative stress as an important factor implicated in all stages of the multistep carcinogenic process: initiation, promotion, and progression. In recent years, ambient air pollution by particulate matter (PM) has been cataloged as a cancer risk factor, increasing the incidence of different types of tumors. Epidemiological and toxicological evidence shows how PM-induced oxidative stress could mediate multiple events oriented to carcinogenesis, such as proliferative signaling, evasion of growth suppressors, resistance to cell death, induction of angiogenesis, and activation of invasion/metastasis pathways. In this review, we summarize the findings regarding the involvement of oxidative and genotoxic mechanisms generated by PM in malignant cell transformation. We also discuss the importance of new approaches oriented to studying the development of tumors associated with PM with more accuracy, pursuing the goal of weighing the impact of oxidative stress and genotoxicity as one of the main mechanisms associated with its carcinogenic potential.

Mexican Colorectal Cancer Research Consortium (MEX-CCRC): Etiology, Diagnosis/Prognosis, and Innovative Therapies.

In 2013, recognizing that Colorectal Cancer (CRC) is the second leading cause of death by cancer worldwide and that it was a neglected disease increasing rapidly in Mexico, the community of researchers at the Biomedicine Research Unit of the Facultad de Estudios Superiores Iztacala from the Universidad Nacional Autónoma de México (UNAM) established an intramural consortium that involves a multidisciplinary group of researchers, technicians, and postgraduate students to contribute to the understanding of this pathology in Mexico. This article is about the work developed by the Mexican Colorectal Cancer Research Consortium (MEX-CCRC): how the Consortium was created, its members, and its short- and long-term goals. Moreover, it is a narrative of the accomplishments of this project. Finally, we reflect on possible strategies against CRC in Mexico and contrast all the data presented with another international strategy to prevent and treat CRC. We believe that the Consortium's characteristics must be maintained to initiate a national strategy, and the reported data could be useful to establish future collaborations with other countries in Latin America and the world.

Food-grade titanium dioxide decreases hematocrit and hemoglobin and increases compulsive-like behavior in male mice.

Food-grade titanium dioxide (E171) is widely used as a food additive, and it is known that after oral consumption, E171 is translocated into the bloodstream reaching the highest titanium level at 6 h. E171 is accumulated in some organs triggering toxicity, but the effects on the blood parameters after oral consumption have been less studied. Recently, evidence shows that oral exposure to E171 induces behavioral signs of anxiety and depression. The relation between blood alterations and psychiatric disorders has been previously demonstrated. However, the oral exposure to E171 effects on alterations in blood parameters and effects linked to alterations in animal behavior has not been explored. In this short communication, we aimed to investigate the effects of E171 on specific blood parameters (hematocrit, hemoglobin, number of erythrocytes, and leukocytes) and anxiety and compulsive-like behavior in males and females orally exposed to ~5 mg/kg for 4 weeks. The results showed that E171 decreased hematocrit and hemoglobin in male but not in female mice while leukocyte and erythrocyte count remained unaltered. Oral consumption of E171 decreased the levels of anxiety-like behavior in females but not in male mice, while compulsive-like behavior was increased in both male and female mice.

Nucleotide Excision Repair Pathway Activity Is Inhibited by Airborne Particulate Matter (PM10) through XPA Deregulation in Lung Epithelial Cells.

Airborne particulate matter with a diameter size of ≤10 µm (PM10) is a carcinogen that contains polycyclic aromatic hydrocarbons (PAH), which form PAH-DNA adducts. However, the way in which these adducts are managed by DNA repair pathways in cells exposed to PM10 has been partially described. We evaluated the effect of PM10 on nucleotide excision repair (NER) activity and on the levels of different proteins of this pathway that eliminate bulky DNA adducts. Our results showed that human lung epithelial cells (A549) exposed to 10 µg/cm2 of PM10 exhibited PAH-DNA adducts as well as an increase in RAD23 and XPD protein levels (first responders in NER). In addition, PM10 increased the levels of H4K20me2, a recruitment signal for XPA. However, we observed a decrease in total and phosphorylated XPA (Ser196) and an increase in phosphatase WIP1, aside from the absence of XPA-RPA complex, which participates in DNA-damage removal. Additionally, an NER activity assay demonstrated inhibition of the NER functionality in cells exposed to PM10, indicating that XPA alterations led to deficiencies in DNA repair. These results demonstrate that PM10 exposure induces an accumulation of DNA damage that is associated with NER inhibition, highlighting the role of PM10 as an important contributor to lung cancer.

Somatic Mutational Landscape in Mexican Patients: CDH1 Mutations and chr20q13.33 Amplifications Are Associated with Diffuse-Type Gastric Adenocarcinoma.

The Hispanic population, compared with other ethnic groups, presents a more aggressive gastric cancer phenotype with higher frequency of diffuse-type gastric adenocarcinoma (GA); this could be related to the mutational landscape of GA in these patients. Using whole-exome sequencing, we sought to present the mutational landscape of GA from 50 Mexican patients who were treated at The Instituto Nacional de Cancerología from 2019 to 2020. We performed a comprehensive statistical analysis to explore the relationship of the genomic variants and clinical data such as tumor histology and presence of signet-ring cell, H. pylori, and EBV. We describe a potentially different mutational landscape between diffuse and intestinal GA in Mexican patients. Patients with intestinal-type GA tended to present a higher frequency of NOTCH1 mutations, copy number gains in cytobands 13.14, 10q23.33, and 12q25.1, and copy number losses in cytobands 7p12, 14q24.2, and 11q13.1; whereas patients with diffuse-type GA tended to present a high frequency of CDH1 mutations and CNV gains in cytobands 20q13.33 and 22q11.21. This is the first description of a mutational landscape of GA in Mexican patients to better understand tumorigenesis in Hispanic patients and lay the groundwork for discovering potential biomarkers and therapeutic targets.

STAT1 Is Required for Decreasing Accumulation of Granulocytic Cells via IL-17 during Initial Steps of Colitis-Associated Cancer.

Signal transducer and activator of transcription 1 (STAT1) acts as a tumor suppressor molecule in colitis-associated colorectal cancer (CAC), particularly during the very early stages, modulating immune responses and controlling mechanisms such as apoptosis and cell proliferation. Previously, using an experimental model of CAC, we reported increased intestinal cell proliferation and faster tumor development, which were consistent with more signs of disease and damage, and reduced survival in STAT1-/- mice, compared with WT counterparts. However, the mechanisms through which STAT1 might prevent colorectal cancer progression preceded by chronic inflammation are still unclear. Here, we demonstrate that increased tumorigenicity related to STAT1 deficiency could be suppressed by IL-17 neutralization. The blockade of IL-17 in STAT1-/- mice reduced the accumulation of CD11b+Ly6ClowLy6G+ cells resembling granulocytic myeloid-derived suppressor cells (MDSCs) in both spleen and circulation. Additionally, IL-17 blockade reduced the recruitment of neutrophils into intestinal tissue, the expression and production of inflammatory cytokines, and the expression of intestinal STAT3. In addition, the anti-IL-17 treatment also reduced the expression of Arginase-1 and inducible nitric oxide synthase (iNOS) in the colon, both associated with the main suppressive activity of MDSCs. Thus, a lack of STAT1 signaling induces a significant change in the colonic microenvironment that supports inflammation and tumor formation. Anti-IL-17 treatment throughout the initial stages of CAC related to STAT1 deficiency abrogates the tumor formation possibly caused by myeloid cells.

Particulate Matter (PM10) Promotes Cell Invasion through Epithelial-Mesenchymal Transition (EMT) by TGF-ß Activation in A549 Lung Cells.

Air pollution presents a major environmental problem, inducing harmful effects on human health. Particulate matter of 10 µm or less in diameter (PM10) is considered an important risk factor in lung carcinogenesis. Epithelial-mesenchymal transition (EMT) is a regulatory program capable of inducing invasion and metastasis in cancer. In this study, we demonstrated that PM10 treatment induced phosphorylation of SMAD2/3 and upregulation of SMAD4. We also reported that PM10 increased the expression and protein levels of TGFB1 (TGF-ß), as well as EMT markers SNAI1 (Snail), SNAI2 (Slug), ZEB1 (ZEB1), CDH2 (N-cadherin), ACTA2 (α-SMA), and VIM (vimentin) in the lung A549 cell line. Cell exposed to PM10 also showed a decrease in the expression of CDH1 (E-cadherin). We also demonstrated that expression levels of these EMT markers were reduced when cells are transfected with small interfering RNAs (siRNAs) against TGFB1. Interestingly, phosphorylation of SMAD2/3 and upregulation of SMAD induced by PM10 were not affected by transfection of TGFB1 siRNAs. Finally, cells treated with PM10 exhibited an increase in the capacity of invasiveness because of EMT induction. Our results provide new evidence regarding the effect of PM10 in EMT and the acquisition of an invasive phenotype, a hallmark necessary for lung cancer progression.

Corrigendum to "Macrophage Migration Inhibitory Factor Promotes the Interaction between the Tumor, Macrophages, and T Cells to Regulate the Progression of Chemically Induced Colitis-Associated Colorectal Cancer".

[This corrects the article DOI: 10.1155/2019/2056085.].

Airborne Particulate Matter (PM10) Inhibits Apoptosis through PI3K/AKT/FoxO3a Pathway in Lung Epithelial Cells: The Role of a Second Oxidant Stimulus.

Outdoor particulate matter (PM10) exposure is carcinogenic to humans. The cellular mechanism by which PM10 is associated specifically with lung cancer includes oxidative stress and damage to proteins, lipids, and DNA in the absence of apoptosis, suggesting that PM10 induces cellular survival. We aimed to evaluate the PI3K/AKT/FoxO3a pathway as a mechanism of cell survival in lung epithelial A549 cells exposed to PM10 that were subsequently challenged with hydrogen peroxide (H2O2). Our results showed that pre-exposure to PM10 followed by H2O2, as a second oxidant stimulus increased the phosphorylation rate of pAKTSer473, pAKTThr308, and pFoxO3aSer253 2.5-fold, 1.8-fold, and 1.2-fold, respectively. Levels of catalase and p27kip1, which are targets of the PIK3/AKT/FoxO3a pathway, decreased 38.1% and 62.7%, respectively. None of these changes had an influence on apoptosis; however, the inhibition of PI3K using the LY294002 compound revealed that the PI3K/AKT/FoxO3a pathway was involved in apoptosis evasion. We conclude that nontoxic PM10 exposure predisposes lung epithelial cell cultures to evade apoptosis through the PI3K/AKT/FoxO3a pathway when cells are treated with a second oxidant stimulus.

Possible Adverse Effects of Food Additive E171 (Titanium Dioxide) Related to Particle Specific Human Toxicity, Including the Immune System.

Titanium dioxide (TiO2) is used as a food additive (E171) and can be found in sauces, icings, and chewing gums, as well as in personal care products such as toothpaste and pharmaceutical tablets. Along with the ubiquitous presence of TiO2 and recent insights into its potentially hazardous properties, there are concerns about its application in commercially available products. Especially the nano-sized particle fraction (<100 nm) of TiO2 warrants a more detailed evaluation of potential adverse health effects after ingestion. A workshop organized by the Dutch Office for Risk Assessment and Research (BuRO) identified uncertainties and knowledge gaps regarding the gastrointestinal absorption of TiO2, its distribution, the potential for accumulation, and induction of adverse health effects such as inflammation, DNA damage, and tumor promotion. This review aims to identify and evaluate recent toxicological studies on food-grade TiO2 and nano-sized TiO2 in ex-vivo, in-vitro, and in-vivo experiments along the gastrointestinal route, and to postulate an Adverse Outcome Pathway (AOP) following ingestion. Additionally, this review summarizes recommendations and outcomes of the expert meeting held by the BuRO in 2018, in order to contribute to the hazard identification and risk assessment process of ingested TiO2.

Use of STAT6 Phosphorylation Inhibitor and Trimethylglycine as New Adjuvant Therapies for 5-Fluorouracil in Colitis-Associated Tumorigenesis.

Colorectal cancer (CRC) is one of the most widespread and deadly types of neoplasia around the world, where the inflammatory microenvironment has critical importance in the process of tumor growth, metastasis, and drug resistance. Despite its limited effectiveness, 5-fluorouracil (5-FU) is the main drug utilized for CRC treatment. The combination of 5-FU with other agents modestly increases its effectiveness in patients. Here, we evaluated the anti-inflammatory Trimethylglycine and the Signal transducer and activator of transcription (STAT6) inhibitor AS1517499, as possible adjuvants to 5-FU in already established cancers, using a model of colitis-associated colon cancer (CAC). We found that these adjuvant therapies induced a remarkable reduction of tumor growth when administrated together with 5-FU, correlating with a reduction in STAT6-phosphorylation. This reduction upgraded the effect of 5-FU by increasing both levels of apoptosis and markers of cell adhesion such as E-cadherin, whereas decreased epithelial-mesenchymal transition markers were associated with aggressive phenotypes and drug resistance, such as ß-catenin nuclear translocation and Zinc finger protein SNAI1 (SNAI1). Additionally, Il-10, Tgf-ß, and Il-17a, critical pro-tumorigenic cytokines, were downmodulated in the colon by these adjuvant therapies. In vitro assays on human colon cancer cells showed that Trimethylglycine also reduced STAT6-phosphorylation. Our study is relatively unique in focusing on the effects of the combined administration of AS1517499 and Trimethylglycine together with 5-FU on already established CAC which synergizes to markedly reduce the colon tumor load. Together, these data point to STAT6 as a valuable target for adjuvant therapy in colon cancer.

Helminth-derived molecules inhibit colitis-associated colon cancer development through NF-κB and STAT3 regulation.

Inflammation is currently considered a hallmark of cancer and plays a decisive role in different stages of tumorigenesis, including initiation, promotion, progression, metastasis and resistance to antitumor therapies. Colorectal cancer is a disease widely associated with local chronic inflammation. Additionally, extrinsic factors such as infection may beneficially or detrimentally alter cancer progression. Several reports have noted the ability of various parasitic infections to modulate cancer development, favoring tumor progression in many cases and inhibiting tumorigenesis in others. The aim of our study was to determine the effects of excreted/secreted products of the helminth Taenia crassiceps (TcES) as a treatment in a murine model of colitis-associated colon cancer (CAC). Here, we found that after inducing CAC, treatment with TcES was able to reduce inflammatory cytokines such as IL-1ß, TNF-α, IL-33 and IL-17 and significantly attenuate colon tumorigenesis. This effect was associated with the inhibition of signal transducer and activator of transcription 3 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) phosphorylation. Furthermore, we determined that TcES interfered with LPS-induced NF-κB p65 activation in human colonic epithelial cell lines in a Raf-1 proto-oncogene-dependent manner. Moreover, in three-dimensional cultures, TcES promoted reorganization of the actin cytoskeleton, altering cell morphology and forming colonospheres, features associated with a low grade of aggressiveness. Our study demonstrates a remarkable effect of helminth-derived molecules on suppressing ongoing colorectal cancer by downregulating proinflammatory and protumorigenic signaling pathways.

Macrophage Migration Inhibitory Factor Promotes the Interaction between the Tumor, Macrophages, and T Cells to Regulate the Progression of Chemically Induced Colitis-Associated Colorectal Cancer.

Colitis-associated colorectal cancer (CRC) development has been shown to be related to chronically enhanced inflammation. Macrophage migration inhibitory factor (MIF) is an inflammatory mediator that favors inflammatory cytokine production and has chemotactic properties for the recruitment of macrophages (Møs) and T cells. Here, we investigated the role of MIF in the inflammatory response and recruitment of immune cells in a murine model of chemical carcinogenesis to establish the impact of MIF on CRC genesis and malignancy. We used BALB/c MIF-knockout (MIF-/-) and wild-type (WT) mice to develop CRC by administering intraperitoneal (i.p.) azoxymethane and dextran sodium sulfate in drinking water. Greater tumor burdens were observed in MIF-/- mice than in WT mice. Tumors from MIF-/- mice were histologically identified to be more aggressive than tumors from WT mice. The localization of MIF suggests that it is also involved in cell differentiation. The relative gene expression of il-17, measured by real-time PCR, was higher in MIF-/- CRC mice, compared to the WT CRC and healthy MIF-/- mice. Importantly, compared to the WT intestinal epithelium, lower percentages of tumor-associated Møs were found in the MIF-/- intestinal epithelium. These results suggest that MIF plays a role in controlling the initial development of CRC by attracting Møs to the tumor, which is a condition that favors the initial antitumor responses.

Food-grade titanium dioxide (E171) by solid or liquid matrix administration induces inflammation, germ cells sloughing in seminiferous tubules and blood-testis barrier disruption in mice.

Food-grade titanium dioxide labeled as E171 has been approved for human consumption by the Food and Drug Administration (USA) and by the European Union for five decades. However, titanium dioxide has been classified as a possible carcinogen for humans by the International Agency of Research in Cancer raising concerns of its oral intake and the translocation to bloodstream, which could disturb barriers such as the blood-testis barrier. There is evidence that titanium dioxide by intragastric/intraperitoneal/intravenous administration induced alterations on testosterone levels, testicular function and architecture, but studies of the E171 effects on the testicle structure and blood-testis barrier are limited. E171 is contained not only in foods in liquid matrix but also in solid ones, which can exert different biological effects. We aimed to compare the effects of E171 consumption in a solid matrix (0.1%, 0.5% and 1% in pellets) and liquid suspension (5 mg/kg body weight) on testis structure, inflammation infiltrate and blood-testis barrier disruption of male BALB/c mice. Results showed that none of the administration routes had influence on body weight but an increase in germ cell sloughing and the infiltrate of inflammatory cells in seminiferous tubules, together with disruption of the blood-testis barrier were similar in testis of both groups even if the dose received in mice in liquid matrix was 136 or 260 times lower than the dose reached by oral intake in solid E171 pellets in 0.5% E171 and 1% E171, respectively. This study highlights the attention on matrix food containing E171 and possible adverse effects on testis when E171 is consumed in a liquid matrix.

Deciphering the Code between Air Pollution and Disease: The Effect of Particulate Matter on Cancer Hallmarks.

Air pollution has been recognized as a global health problem, causing around 7 million deaths worldwide and representing one of the highest environmental crises that we are now facing. Close to 30% of new lung cancer cases are associated with air pollution, and the impact is more evident in major cities. In this review, we summarize and discuss the evidence regarding the effect of particulate matter (PM) and its impact in carcinogenesis, considering the "hallmarks of cancer" described by Hanahan and Weinberg in 2000 and 2011 as a guide to describing the findings that support the impact of particulate matter during the cancer continuum.

Titanium dioxide food additive (E171) induces ROS formation and genotoxicity: contribution of micro and nano-sized fractions.

Since 1969, the European Union approves food-grade titanium dioxide (TiO2), also known as E171 colouring food additive. E171 is a mixture of micro-sized particles (MPs) and nano-sized particles (NPs). Previous studies have indicated adverse effects of oral exposure to E171, i.e. facilitation of colon tumour growth. This could potentially be partially mediated by the capacity to induce reactive oxygen species (ROS). The aim of the present study is to determine whether E171 exposure induces ROS formation and DNA damage in an in vitro model using human Caco-2 and HCT116 cells and to investigate the contribution of the separate MPs and NPs TiO2 fractions to these effects. After suspension of the particles in Hanks' balanced salt solution buffer and cell culture medium with either bovine serum albumin (BSA) or foetal bovine serum, characterization of the particles was performed by dynamic light scattering, ROS formation was determined by electron spin/paramagnetic resonance spectroscopy and DNA damage was determined by the comet and micronucleus assays. The results showed that E171, MPs and NPs are stable in cell culture medium with 0.05% BSA. The capacity for ROS generation in a cell-free environment was highest for E171, followed by NPs and MPs. Only MPs were capable to induce ROS formation in exposed Caco-2 cells. E171, MPs and NPs all induced single-strand DNA breaks. Chromosome damage was shown to be induced by E171, as tested with the micronucleus assay in HCT116 cells. In conclusion, E171 has the capability to induce ROS formation in a cell-free environment and E171, MPs and NPs have genotoxic potential. The capacity of E171 to induce ROS formation and DNA damage raises concerns about potential adverse effects associated with E171 (TiO2) in food.