Oral Exposure to Titanium Dioxide E171 and Zinc Oxide Nanoparticles Induces Multi-Organ Damage in Rats: Role of Ceramide.

Food-grade titanium dioxide (E171) and zinc oxide nanoparticles (ZnO NPs) are common food additives for human consumption. We examined multi-organ toxicity of both compounds on Wistar rats orally exposed for 90 days. Rats were divided into three groups: (1) control (saline solution), (2) E171-exposed, and (3) ZnO NPs-exposed.

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.

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.

Early detection of colorectal cancer somatic mutations using cfDNA liquid biopsies in a murine carcinogenesis model.

Colorectal cancer (CRC) is one of the top five cancers in incidence and mortality worldwide. The early detection of this neoplasm through analysis of circulating free DNA (cfDNA), which carries tumor genetic alterations, as a liquid biopsy, could have a major impact in enhancing early detection and reducing the mortality rate. The aim of this work was to demonstrate the feasibility of using cfDNA as a liquid biopsy for the early detection of CRC.

The Evolution of Clinically Aggressive Triple-Negative Breast Cancer Shows a Large Mutational Diversity and Early Metastasis to Lymph Nodes.

In triple-negative breast cancer (TNBC), only 30% of patients treated with neoadjuvant chemotherapy achieve a pathological complete response after treatment and more than 90% die due to metastasis formation. The diverse clinical responses and metastatic developments are attributed to extensive intrapatient genetic heterogeneity and tumor evolution acting on this neoplasm. In this work, we aimed to evaluate genomic alterations and tumor evolution in TNBC patients with aggressive disease.

Comprehensive Genomic Profile of Heterogeneous Long Follow-Up Triple-Negative Breast Cancer and Its Clinical Characteristics Shows DNA Repair Deficiency Has Better Prognostic.

Triple-negative breast cancer (TNBC) presents a marked diversity at the molecular level, which promotes a clinical heterogeneity that further complicates treatment. We performed a detailed whole exome sequencing profile of 29 Mexican patients with long follow-up TNBC to identify genomic alterations associated with overall survival (OS), disease-free survival (DFS), and pathologic complete response (PCR), with the aim to define their role as molecular predictive factors of treatment response and prognosis. We detected 31 driver genes with pathogenic mutations in (53%), (27%), (9%), (9%), and (9%), and 16 operative mutational signatures.

Astrocytes Are More Vulnerable than Neurons to Silicon Dioxide Nanoparticle Toxicity in Vitro.

Some studies have shown that silicon dioxide nanoparticles (SiO-NPs) can reach different regions of the brain and cause toxicity; however, the consequences of SiO-NPs exposure on the diverse brain cell lineages is limited. We aimed to investigate the neurotoxic effects of SiO-NP (0-100 µg/mL) on rat astrocyte-rich cultures or neuron-rich cultures using scanning electron microscopy, Attenuated Total Reflection-Fourier Transform Infrared spectroscopy (ATR-FTIR), FTIR microspectroscopy mapping (IQ mapping), and cell viability tests. SiO-NPs were amorphous particles and aggregated in saline and culture media.

Latin American Study of Hereditary Breast and Ovarian Cancer : A Genomic Epidemiology Approach.

Hereditary Breast and Ovarian Cancer (HBOC) syndrome is responsible for ~5-10% of all diagnosed breast and ovarian cancers. Breast cancer is the most common malignancy and the leading cause of cancer-related mortality among women in Latin America (LA). The main objective of this study was to develop a comprehensive understanding of the genomic epidemiology of HBOC throughout the establishment of The Latin American consortium for HBOC-LACAM, consisting of specialists from 5 countries in LA and the description of the genomic results from the first phase of the study.

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.

Comprehensive Analysis of Germline Variants in Mexican Patients with Hereditary Breast and Ovarian Cancer Susceptibility.

Hereditary breast and ovarian cancer syndrome (HBOC) represents 5⁻10% of all patients with breast cancer and is associated with high-risk pathogenic alleles in genes, but only for 25% of cases. We aimed to find new pathogenic alleles in a panel of 143 cancer-predisposing genes in 300 Mexican cancer patients with suspicion of HBOC and 27 high-risk patients with a severe family history of cancer, using massive parallel sequencing. We found pathogenic variants in 23 genes, including .

Renal damage in the metabolic syndrome (MetSx): Disorders implicated.

The prevalence of metabolic syndrome is increasing worldwide and has become a risk factor for the development of chronic kidney disease. The complex linkage between metabolic syndrome and chronic kidney disease is under research and the factors involved beyond the biological pathogenesis include demographic, sociological and psychological factors that are related to the metabolic syndrome prevalence. The social context of disease causation is as relevant to today's clinical scientist and practitioner as biomarker-directed risk stratification and therapy.

Applications and Risks of Nanomaterials Used in Regenerative Medicine, Delivery Systems, Theranostics, and Therapy.

Recent advances in nanotechnology have transformed the biomedicine field, in which the use of engineered nanomaterials (ENMs) has provided the foundation for novel applications. For this reason, the number of ENMs has increased rapidly, and here we provide a classification of ENMs based on chemical composition and biomedical applications, which include regenerative medicine, delivery systems, theranostics, and therapy. These have been identified as the most advanced and promising areas for further studies with humans.

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.

Difficulties in establishing regulations for engineered nanomaterials and considerations for policy makers: avoiding an unbalance between benefits and risks.

Current evidence of engineered nanomaterials' (ENM) toxicity has led to a latent concern about hazards for both humans and the environment. For this reason, some efforts have been made to suggest frameworks or other guidance to regulate ENM handling; however, the real exposure risk to humans has not been well established. The aims of this work were to analyze the difficulties in establishing regulations for ENM and to discuss some considerations that may be helpful for policy makers involved in the regulation of ENM.

Mitochondria as a target in the therapeutic properties of curcumin.

Curcumin, a phenolic compound extracted from Curcuma longa, is commonly used in Asia as a spice and pigment and has several biological functions, particularly antioxidant properties. It has been reported that curcumin exhibits bifunctional antioxidant properties related to its capability to react directly with reactive oxygen species (ROS) and also to its ability to induce the expression of cytoprotective and antioxidant proteins through the transcription factor nuclear factor-erythroid-2-related factor 2 (Nrf2). Recently, it has been postulated that the mitochondrial function and metabolism are associated with Nrf2 and that curcumin has shown activities against mitochondrial dysfunction.

Titanium dioxide nanoparticles induce strong oxidative stress and mitochondrial damage in glial cells.

Titanium dioxide nanoparticles (TiO2 NPs) are widely used in the chemical, electrical, and electronic industries. TiO2 NPs can enter directly into the brain through the olfactory bulb and can be deposited in the hippocampus region; therefore, we determined the toxic effect of TiO2 NPs on rat and human glial cells, C6 and U373, respectively. We evaluated some events related to oxidative stress: (1) redox-signaling mechanisms by oxidation of 2',7'-dichlorodihydrofluorescein diacetate; (2) peroxidation of lipids by cis-parinaric acid; (3) antioxidant enzyme expression by PCR in real time; and (4) mitochondrial damage by MitoTracker Green FM staining and Rh123.

Renoprotective effect of the antioxidant curcumin: Recent findings.

For years, there have been studies based on the use of natural compounds plant-derived as potential therapeutic agents for various diseases in humans. Curcumin is a phenolic compound extracted from Curcuma longa rhizome commonly used in Asia as a spice, pigment and additive. In traditional medicine of India and China, curcumin is considered as a therapeutic agent used in several foods.

Titanium dioxide nanoparticles inhibit proliferation and induce morphological changes and apoptosis in glial cells.

Titanium dioxide nanoparticles (TiO(2) NPs) are widely used in the chemical, electrical and electronic industries. TiO(2) NPs can enter directly into the brain through the olfactory bulb and be deposited in the hippocampus region. We determined the effect of TiO(2) NPs on rat and human glial cells, C6 and U373, respectively.

Protective effect of sulforaphane against oxidative stress: recent advances.

Sulforaphane [1-isothiocyanate-(4R)-(methylsulfinyl)butane] is a natural dietary isothiocyanate produced by the enzymatic action of the myrosinase on glucopharanin, a 4-methylsulfinylbutyl glucosinolate contained in cruciferous vegetables of the genus Brassica such as broccoli, brussel sprouts, and cabbage. Studies on this compound is increasing because its anticarcinogenic and cytoprotective properties in several in vivo experimental paradigms associated with oxidative stress such as focal cerebral ischemia, brain inflammation, intracerebral hemorrhage, ischemia and reperfusion induced acute renal failure, cisplatin induced-nephrotoxicity, streptozotocin-induced diabetes, carbon tetrachloride-induced hepatotoxicity and cardiac ischemia and reperfusion. This protective effect also has been observed in in vitro studies in different cell lines such as human neuroblastoma SH-SY5Y, renal epithelial proximal tubule LLC-PK1 cells and aortic smooth muscle A10 cells.

PJ34, a poly adenosine diphosphate-ribose polymerase inhibitor, attenuates chromate-induced nephrotoxicity.

Potassium dichromate (K(2)Cr(2)O(7))-induced nephrotoxicity is associated with oxidative stress. In addition, the activation of the polyadenosine diphosphate-ribose [poly(ADP-ribose)] polymerase-1 (PARP-1) plays a role in the pathophysiology of some diseases associated with oxidative stress. To clarify the potential role of PARP-1 in this experimental model, N-(6-oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-dimethyacetamide HCl (PJ34), a highly specific inhibitor of this enzyme, was used.