Food-grade titanium dioxide and zinc oxide nanoparticles induce toxicity and cardiac damage after oral exposure in rats.

BACKGROUND: Metallic nanoparticles (NPs) are widely used as food additives for human consumption. NPs reach the bloodstream given their small size, getting in contact with all body organs and cells. NPs have adverse effects on the respiratory and intestinal tract; however, few studies have focused on the toxic consequences of orally ingested metallic NPs on the cardiovascular system. Here, the effects of two food-grade additives on the cardiovascular system were analyzed. METHODS: Titanium dioxide labeled as E171 and zinc oxide (ZnO) NPs were orally administered to Wistar rats using an esophageal cannula at 10 mg/kg bw every other day for 90 days. We evaluated cardiac cell morphology and death, expression of apoptotic and autophagic proteins in cardiac mitochondria, mitochondrial dysfunction, and concentration of metals on cardiac tissue. RESULTS: Heart histology showed important morphological changes such as presence of cellular infiltrates, collagen deposition and mitochondrial alterations in hearts from rats exposed to E171 and ZnO NPs. Intracellular Cyt-C levels dropped, while TUNEL positive cells increased. No significant changes in the expression of inflammatory cytokines were detected. Both NPs altered mitochondrial function indicating cardiac dysfunction, which was associated with an elevated concentration of calcium. ZnO NPs induced expression of caspases 3 and 9 and two autophagic proteins, LC3B and beclin-1, and had the strongest effect compared to E171. CONCLUSIONS: E171 and ZnO NPs induce adverse cardiovascular effects in rats after 90 days of exposure, thus food intake containing these additives, should be taken into consideration, since they translocate into the bloodstream and cause cardiovascular damage.

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.

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.

Zinc Oxide Nanoparticles Induce Toxicity in H9c2 Rat Cardiomyoblasts.

Zinc oxide nanoparticles (ZnO NPs) are widely used in the cosmetic industry. They are nano-optical and nano-electrical devices, and their antimicrobial properties are applied in food packaging and medicine. ZnO NPs penetrate the body through inhalation, oral, and dermal exposure and spread through circulation to various systems and organs. Since the cardiovascular system is one of the most vulnerable systems, in this work, we studied ZnO NPs toxicity in H9c2 rat cardiomyoblasts. Cardiac cells were exposed to different concentrations of ZnO NPs, and then the morphology, proliferation, viability, mitochondrial membrane potential (ΔΨm), redox state, and protein expression were measured. Transmission electron microscopy (TEM) and hematoxylin-eosin (HE) staining showed strong morphological damage. ZnO NPs were not observed inside cells, suggesting that Zn2+ ions were internalized, causing the damage. ZnO NPs strongly inhibited cell proliferation and MTT reduction at 10 and 20 µg/cm2 after 72 h of treatment. ZnO NPs at 20 µg/cm2 elevated DCF fluorescence, indicating alterations in the cellular redox state associated with changes in ΔΨm and cell death. ZnO NPs also reduced the intracellular expression of troponin I and atrial natriuretic peptide. ZnO NPs are toxic for cardiac cells; therefore, consumption of products containing them could cause heart damage and the development of cardiovascular diseases.

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.

Novel thiosemicarbazones induce high toxicity in estrogen-receptor-positive breast cancer cells (MCF7) and exacerbate cisplatin effectiveness in triple-negative breast (MDA-MB231) and lung adenocarcinoma (A549) cells.

Cis-diamminedichloroplatinum(II) (CDDP), known as cisplatin, has been extensively used against breast cancer, which is the most frequent cancer among women, and lung cancer, the leading cancer that causes death worldwide. Novel compounds such as thiazole derivatives have exhibited antiproliferative activity, suggesting they could be useful against cancer treatment. Herein, we synthesized two novel thiosemicarbazones and an aldehyde to combine with CDDP to enhance efficacy against ER-positive breast MCF7 cancer cells, triple-negative/basal-B mammary carcinoma cells (MDA-MB231) and lung adenocarcinoma (A549) human cells. We synthesized 2,3,5,6-tetrafluoro-4-(2-mercaptoetanothiolyl)benzaldehyde (ALD), 5-[(2,3,5,6-tetrafluoro-4-(trifluoromethyl)phenyl)thio]-2-furaldehyde thiosemicarbazone (TSC1) and 5-[(4-(trifluoromethyl)phenyl)thio]-2-furaldehyde thiosemicarbazone (TSC2) and used them alone or in combination with subtoxic CDDP concentrations to evaluate cytotoxicity, cytoskeleton integrity and mitochondrial function. We found that none of the synthesized compounds improved CDDP activity against MCF7 cell cultures; however, TSC2 was effective in enhancing the cytotoxicity of CDDP against MDA-MB231 and A549 cancer cell cultures. We demonstrated that the cytotoxic effect is related to the TSC2 capacity to induce disruption in the cytoskeleton network and to decrease mitochondrial function.

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.

A Novel Positive Regulator of the Early Stages of Root Nodule Symbiosis Identified by Phosphoproteomics.

Signals and signaling pathways underlying the symbiosis between legumes and rhizobia have been studied extensively over the past decades. In a previous phosphoproteomic study on the Medicago truncatula-Sinorhizobium meliloti symbiosis, we identified plant proteins that are differentially phosphorylated upon the perception of rhizobial signals, called Nod factors. In this study, we provide experimental evidence that one of these proteins, Early Phosphorylated Protein 1 (EPP1), is required for the initiation of this symbiosis. Upon inoculation with rhizobia, MtEPP1 expression was induced in curled root hairs. Down-regulation of MtEPP1 in M. truncatula roots almost abolished calcium spiking, reduced the expression of essential symbiosis-related genes (MtNIN, MtNF-YB1, MtERN1 and MtENOD40) and strongly decreased nodule development. Phylogenetic analyses revealed that orthologs of MtEPP1 are present in legumes and specifically in plant species able to host arbuscular mycorrhizal fungi, suggesting a possible role in this association too. Short chitin oligomers induced the phosphorylation of MtEPP1 like Nod factors. However, the down-regulation of MtEPP1 affected the colonization of M. truncatula roots by arbuscular mycorrhizal fungi only moderately. Altogether, these findings indicate that MtEPP1 is essential for the establishment of the legume-rhizobia symbiosis but might plays a limited role in the arbuscular mycorrhizal symbiosis.

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.

Secretome derived from breast tumor cell lines alters the morphology of human umbilical vein endothelial cells.

Metastases, responsible for most of the solid tumor associated deaths, require angiogenesis and changes in endothelial cells. In this work, the effect of the secretomes of three breast tumor cell lines (MCF-7, MDA-MB-231 and ZR-75-30) on human umbilical vein endothelial cells (HUVEC) morphology was investigated. HUVEC treated with secretomes from breast cells were analyzed by confocal and time-lapse microscopy. Secretomes from ZR-75-30 and MDA-MB-231 cells modify the morphology and adhesion of HUVEC. These changes may provoke the loss of endothelial monolayer integrity. In consequence, tumor cells could have an increased access to circulation, which would then enhance metastasis.

Cardiolipin deficiency causes a dissociation of the b 6 c:caa 3 megacomplex in B. subtilis membranes.

The associations among respiratory complexes in energy-transducing membranes have been established. In fact, it is known that the Gram-negative bacteria Paracoccus denitrificans and Escherichia coli have respiratory supercomplexes in their membranes. These supercomplexes are important for channeling substrates between enzymes in a metabolic pathway, and the assembly of these supercomplexes depends on the protein subunits and membrane lipids, mainly cardiolipin, which is present in both the mitochondrial inner membrane and bacterial membranes. The Gram-positive bacterium Bacillus subtilis has a branched respiratory chain, in which some complexes generate proton motive force whereas others constitute an escape valve of excess reducing power. Some peculiarities of this respiratory chain are the following: a type II NADH dehydrogenase, a unique b 6 c complex that has a b 6 type cytochrome with a covalently bound heme, and a c-type heme attached to the third subunit, which is similar to subunit IV of the photosynthetic b 6 f complex. Cytochrome c oxygen reductase (caa 3 ) contains a c-type cytochrome on subunit I. We previously showed that the b 6 c and the caa 3 complexes form a supercomplex. Both the b 6 c and the caa 3 together with the quinol oxygen reductase aa 3 generate the proton motive force in B. subtilis. In order to seek proof that this supercomplex is important for bacterial growth in aerobic conditions we compared the b 6 c: caa 3 supercomplex from wild type membranes with membranes from two mutants lacking cardiolipin. Both mutant complexes were found to have similar activity and heme content as the wild type. Clear native electrophoresis showed that mutants lacking cardiolipin had b 6 c:caa 3 supercomplexes of lower mass or even individual complexes after membrane solubilization with digitonin. The use of dodecyl maltoside revealed a more evident difference between wild-type and mutant supercomplexes. Here we provide evidence showing that cardiolipin plays a role in the stability of the b 6 c:caa 3 supercomplex in B. subtilis.

Role of Wasp and the small GTPases RhoA, RhoB, and Cdc42 during capacitation and acrosome reaction in spermatozoa of English guinea pigs.

Cytoskeleton remodeling is necessary for capacitation and the acrosome reaction in spermatozoa. F-actin is located in the acrosome and equatorial region during capacitation, but is relocated in the post-acrosomal region during the acrosome reaction in spermatozoa from bull, rat, mice, and guinea pig. Actin polymerization and relocalization are generally regulated by small GTPases that activate Wasp protein, which coordinates with Arp2/3, profilin I, and profilin II to complete cytoskeletal remodeling. This sequence of events is not completely described in spermatozoa, though. Therefore, the aim of this study was to determine if Wasp interacts with small GTPases (RhoA, RhoB, and Cdc42) and proteins (Arp2/3, profilin I, and profilin II) that co-localize with F-actin during capacitation and the acrosome reaction in English guinea pig spermatozoa obtained from the vas deferens. The spermatozoa were capacitated in calcium-free medium, incubated with an activator or an inhibitor of GTPases, and then induced to acrosome react using calcium. The distribution patterns of F-actin were compared to the patterns of Wasp and its putative interaction partners: Wasp and RhoB, but not RhoA or Cdc42, localization overlap with F-actin during capacitation and the acrosome reaction. Activation of small GTPases localized RhoB to the post-acrosomal region whereas their inhibition prevented acrosome exocytosis. Arp2/3 and profilin II appear to interact with Wasp in the post-acrosomal region and flagellum, while profilin I and Wasp could be found in the equatorial region. Thus, Wasp and F-actin distribution overlap during capacitation and acrosome reaction, and small GTPases play an important role in cytoskeleton remodeling during these processes in spermatozoa. Mol. Reprod. Dev. 83: 927-937, 2016 © 2016 Wiley Periodicals, Inc.

Titanium dioxide nanoparticles induce an adaptive inflammatory response and invasion and proliferation of lung epithelial cells in chorioallantoic membrane.

Titanium dioxide nanoparticles (TiO2 NPs) studies have been performed using relatively high NPs concentration under acute exposure and limited studies have compared shape effects. We hypothesized that midterm exposure to low TiO2 NPs concentration in lung epithelial cells induces carcinogenic characteristics modulated partially by NPs shape. To test our hypothesis we synthesized NPs shaped as belts (TiO2-B) using TiO2 spheres (TiO2-SP) purchased from Sigma Aldrich Co. Then, lung epithelial A549 cells were low-exposed (10 µg/cm(2)) to both shapes during 7 days and internalization, cytokine release and invasive potential were determined. Results showed greater TiO2-B effect on agglomerates size, cell size and granularity than TiO2-SP. Agglomerates size in cell culture medium was 310 nm and 454 nm for TiO2-SP and TiO2-B, respectively; TiO2-SP and TiO2-B induced 23% and 70% cell size decrease, respectively, whilst TiO2-SP and TiO2-B induced 7 and 14-fold of granularity increase. NOx production was down-regulated (31%) by TiO2-SP and up-regulated (70%) by TiO2-B. Both NPs induced a transient cytokine release (IL-2, IL-6, IL-8, IL-4, IFN-γ, and TNF-α) after 4 days, but cytokines returned to basal levels in TiO2-SP exposed cells while TiO2-B induced a down-regulation after 7 days. Midterm exposure to both shapes of NPs induced capability to degrade cellular extracellular matrix components from chorioallantoic membrane and Ki-67 marker showed that TiO2-B had higher proliferative potential than TiO2-SP. We conclude that midterm exposure to low NPs concentration of NPs has an impact in the acquisition of new characteristics of exposed cells and NPs shape influences cellular outcome.

Nrf2 protects the lung against inflammation induced by titanium dioxide nanoparticles: A positive regulator role of Nrf2 on cytokine release.

Titanium dioxide nanoparticles (TiO2 NPs) have been classified as possibly carcinogenic to humans and they are an important nanomaterial widely used in pharmaceutical and paint industries. Inhalation is one of the most important routes of exposure in occupational settings. Several experimental models have shown that oxidative stress and inflammation are key mediators of cell damage. In this regard, Nrf2 modulates cytoprotection against oxidative stress and inflammation, however, its role in inflammation induced by TiO2 NPs exposure has been less investigated. The aim of this work was to investigate the role of Nrf2 in the cytokines produced after 4 weeks of TiO2 NPs exposure (5 mg/kg/2 days/week) using wild-type and Nrf2 knockout C57bl6 mice. Results showed that Nrf2 protects against inflammation and oxidative damage induced by TiO2 NPs exposure, however, Nrf2 is a positive mediator in the expression of IFN-γ, TNF-α, and TGF-ß in bronchial epithelium and alveolar space after 4 weeks of exposure. These results suggest that Nrf2 has a central role in up-regulation of cytokines released during inflammation induced by TiO2 NPs and those cytokines are needed to cope with histological alterations in lung tissue.

Decrease in respiratory function and electron transport chain induced by airborne particulate matter (PM10) exposure in lung mitochondria.

Particulate matter, with a mean aerodynamic diameter of ≤10 µm (PM10), exposure is considered as a risk factor for cardiovascular and respiratory diseases. The mechanism of cell damage induced by PM10 exposure is related to mitochondrial alterations. The aim of this work was to investigate the detailed alterations induced by PM10 on mitochondrial function. Since lung tissue is one of the most important targets of PM10 inhalation, isolated mitochondria from lung rat tissue were exposed to PM10 and structural alterations were analyzed by transmission electron microscopy. Mitochondrial function was evaluated by respiratory control index (RCI), membrane potential, adenosine triphosphate (ATP) synthesis, and activity of respiratory chain. Results showed that exposure to PM10 in isolated mitochondria from lung tissue caused enlarged intermembrane spaces and shape alterations, disruption of cristae, and the decrease in dense granules. Oxygraphic traces showed a concentration-dependent decrease in oxygen consumption and RCI. In addition, mitochondrial membrane potential, ATP synthesis, and activity of complexes II and IV showed an increase and decrease, respectively, after PM10 exposure. PM10 exposure induced disruption in structure and function in isolated mitochondria from lung rat tissue.

Food-grade titanium dioxide (E171) differentially affects satiation in mice fed a regular or a high fat diet.

Food-grade titanium dioxide (E171) is a widely used food additive and the toxicity after oral consumption is still under research, although it has been already banned in some countries. The consumption of this additive occurs mainly through ultra-processed food products which also contain high amounts of fat. High fat diets (HFD) impair the physiological system controlling satiation and satiety, which are responsible for control of food intake and energy status. The impact of E171 on animal behavior has been poorly explored and here we hypothesize that E171 could worsen the effects on feeding behavior induced by HFD. Therefore, we aimed to evaluate the effects of E171 on the feeding pattern and the behavioral satiety sequence (BSS) of mice fed with a regular diet (RD) or a HFD after 1 and 16 weeks of exposure. The results showed that RD + E171 increased food intake and feeding time, but the prototypical structure of the BSS pattern (feeding→ grooming-activity → resting), was preserved. Conversely, food consumption was not altered in HFD + E171, but the BSS pattern was disrupted as the animals prolonged resting time and spent less time being active. Our findings suggest that E171 delayed the onset of satiation in mice fed with RD but induced the opposite effect in mice fed with HFD.

Reply to Kaminski, N.E.; Cohen, S.M. Comment on "Bischoff et al. The Effects of the Food Additive Titanium Dioxide (E171) on Tumor Formation and Gene Expression in the Colon of a Transgenic Mouse Model for Colorectal Cancer. Nanomaterials 2022, 12, 1256".

We appreciate the interest in our article describing transcriptome changes in a transgenic mouse model carrying an APC gene mutation and would like to reply to the reader [...].

Correction: Bischoff et al. The Effects of the Food Additive Titanium Dioxide (E171) on Tumor Formation and Gene Expression in the Colon of a Transgenic Mouse Model for Colorectal Cancer. Nanomaterials 2022, 12, 1256.

In the published publication [...].

Effect of the Essential Oils of Bursera morelensis and Lippia graveolens and Five Pure Compounds on the Mycelium, Spore Production, and Germination of Species of Fusarium.

The genus Fusarium causes many diseases in economically important plants. Synthetic agents are used to control postharvest diseases caused by Fusarium, but the use of these synthetic agents generates several problems, making it necessary to develop new alternative pesticides. Essential oils can be used as a new control strategy. The essential oils of Bursera morelensis and Lippia graveolens have been shown to have potent antifungal activity against Fusarium. However, for the adequate management of diseases, as well as the optimization of the use of essential oils, it is necessary to know how essential oils act on the growth and reproduction of the fungus. In this study, the target of action of the essential oils of B. morelensis and L. graveolens and of the pure compounds present in the essential oils (carvacrol, p-cymene, α-phellandrene, α-pinene, and Υ-terpinene) was determined by evaluating the effect on hyphal morphology, as well as on spore production and germination of three Fusarium species. In this work, carvacrol was found to be the compound that produced the highest inhibition of radial growth. Essential oils and pure compounds caused significant damage to hyphal morphology and affected spore production and germination of Fusarium species.