Effect of pesticides on phosphorylation of tau protein, and its influence on Alzheimer's disease.

Alzheimer's disease (AD) is a progressive and neurodegenerative illness which results in alterations in cognitive development. It is characterized by loss/dysfunction of cholinergic neurons, and formation of amyloid plaques, and formation of neurofibrillary tangles, among other changes, due to hyperphosphorylation of tau-protein. Exposure to pesticides in humans occurs frequently due to contact with contaminated food, water, or particles. Organochlorines, organophosphates, carbamates, pyrethroids and neonicotinoids are associated with the most diagnosed incidents of severe cognitive impairment. The aim of this study was to determine the effects of these pesticides on the phosphorylation of tau protein, and its cognitive implications in the development of AD. It was found that exposure to pesticides increased the phosphorylation of tau protein at sites Ser198, Ser199, Ser202, Thr205, Ser396 and Ser404. Contact with these chemicals altered the enzymatic activities of cyclin-dependent kinase 5 and glycogen synthase kinase 3 beta, and protein phosphatase-2A. Moreover, it altered the expression of the microtubule associated protein tau gene, and changed levels of intracellular calcium. These changes affected tau protein phosphorylation and neuroinflammation, and also increased oxidative stress. In addition, the exposed subjects had poor level of performance in tests that involved evaluation of novelty, as test on verbal, non-verbal, spatial memory, attention, and problem-solving skills.

The Association between Pesticide Exposure and the Development of Fronto-Temporal Dementia-Cum-Dissociative Disorders: A Review.

Pesticides are chemicals used in agricultural fields for the prevention or destruction of pests. Inappropriate use of these substances, as well as handling them without using personal protective equipment, may result in serious health problems such as neurodegenerative diseases and mental disorders. Previous studies have demonstrated the adverse effects of pesticides on brain function. However, some researchers have associated pesticide poisoning with the development of disorders such as dissociative amnesia, multiple personality disorders, and depersonalization disorder. The objective of this work was to perform a bibliographic review of the relationship between pesticide poisoning and the development of dissociative disorders. Previous studies suggest that the duration of pesticide exposure is a major determinant in the development of dissociative diseases and disorders. The information obtained in this review suggests that there is no specific relationship between dissociative disorders and pesticide poisoning. However, these results point to associating the most representative symptoms of dissociative disorder (such as amnesia and memory loss) with pesticide exposure. Based on the bibliographic search, possible mechanisms of action were suggested in an attempt to explain a possible association between exposure to pesticides and the appearance of dissociative disorders.

Oral Antiseptics against SARS-CoV-2: A Literature Review.

Dentists are health care workers with the highest risk of exposure to COVID-19, because the oral cavity is considered to be a reservoir for SARS-CoV-2 transmission. The identification of SARS-CoV-2 in saliva, the generation of aerosols, and the proximity to patients during dental procedures are conditions that have led to these health care workers implementing additional disinfection strategies for their protection. Oral antiseptics are widely used chemical substances due to their ability to reduce the number of microorganisms. Although there is still no evidence that they can prevent the transmission of SARS-CoV-2, some preoperative oral antiseptics have been recommended as control measures, by different health institutions worldwide, to reduce the number of microorganisms in aerosols and droplets during dental procedures. Therefore, this review presents the current recommendations for the use of oral antiseptics against SARS-CoV-2 and analyzes the different oral antiseptic options used in dentistry.

Extracellular vesicles from blood of breast cancer women induce angiogenic processes in HUVECs.

Breast cancer is the most frequent malignancy among women in developed countries and the main cause of death related to cancer in women worldwide. Extracellular vesicles (EVs) are vesicles with a variable size enclosed within a phospholipid bilayer that contain a variety of molecules with biological activity. Cancer cells release EVs that induce proliferation, escape from apoptosis, reprogramming energy metabolism, invasion and metastasis. In this study we studied whether EV fractions deprived of platelet EVs from breast cancer women (BC EVs) can mediate cell processes related with angiogenesis in human umbilical vein endothelial cells (HUVECs). Our findings demonstrate that BC EVs enhance migration, invasion and formation of new tubules in HUVECs, compared with EV fractions deprived of platelet EVs from healthy women (Ctrl EVs). In summary, we demonstrate, for the first time, that BC EVs induce cellular processes in HUVECs that participate in angiogenesis.

Genetic profile for the detection of susceptibility to poisoning by exposure to pesticides.

INTRODUCTION: In humans, there are sets of genes that encode enzymes that decrease or increase the risks derived from exposure to pesticides. These include DNA repair genes (XRCC1, OGG1 and XRCC4); pesticide metabolizers (GSTP1 and PON1), and genes that act against oxidative stress (SOD2 and NQO1). OBJECTIVE: The aim of this literature review is to provide information about the genes involved in the defence systems against exposure to pesticides, as well as their polymorphisms, functions, and general characteristics of the encoded enzymes. MATERIAL AND METHODS: Information was obtained from scientific articles published between 2015-2020 in the PubMed database (https://pubmed.ncbi.nlm.nih.gov). RESULTS: Genes related to the defence processes against pesticides present single-nucleotide polymorphisms (SNPs) with allelic variants that affect the expressions or structures of the encoded enzymes, negatively altering their activities. If we knew the genetic profile that includes polymorphisms of DNA-repairing genes, metabolizing genes, and genes against oxidative stress in subjects exposed to pesticides, we would also know about their susceptibility to poisoning caused by these chemicals. CONCLUSIONS: The genes could be used to propose a genetic profile in farmers exposed to various pesticides, including 10 gene polymorphisms involved in susceptibility to various pathologies related to DNA repair, xenobiotic metabolism, and oxidative stress. It could also be useful as a preventive measure to identify susceptibility to pesticide poisoning.

Pentoxifylline Enhances the Apoptotic Effect of Carboplatin in Y79 Retinoblastoma Cells.

BACKGROUND/AIM: Retinoblastoma (RB) is the most common primary intraocular malignancy. Carboplatin (CPt) is a DNA damage-inducing agent that is widely used for the treatment of RB. Unfortunately, this drug also activates the transcription factor nuclear factor-kappa B (NF-ĸB), leading to promotion of tumor survival. Pentoxifylline (PTX) is a drug that inhibits the phosphorylation of I kappa B-alpha (IĸBα) in serines 32 and 36, and this disrupts NF-ĸB activity that promotes tumor survival. The goal of this study was to evaluate the effect of the PTX on the antitumor activity of CPt. MATERIALS AND METHODS: Y79 RB cells were treated with CPt, PTX, or both. Cell viability, apoptosis, loss of mitochondrial membrane potential, the activity of caspase-9, -8, and -3, cytochrome c release, cell-cycle progression, p53, and phosphorylation of IĸBα, and pro- and anti-apoptotic genes were evaluated. RESULTS: Both drugs significantly affected the viability of the Y79 RB cells in a time- and dose-dependent manner. The PTX+CPt combination exhibited the highest rate of apoptosis, a decrease in cell viability and significant caspase activation, as well as loss of mitochondrial membrane potential, release of cytochrome c, and increased p53 protein levels. Cells treated with PTX alone displayed decreased I kappa B-alpha phosphorylation, compared to the CPt treated group. In addition, the PTX+CPt combination treatment induced up-regulation of the proapoptotic genes Bax, Bad, Bak, and caspases- 3, -8, and -9, compared to the CPt and PTX individual treated groups. CONCLUSION: PTX induces apoptosis per se and increases the CPt-induced apoptosis, augmenting its antitumor effectiveness.

Linoleic acid induces migration and invasion through FFAR4- and PI3K-/Akt-dependent pathway in MDA-MB-231 breast cancer cells.

An increased risk of developing breast cancer has been associated with high levels of dietary fat intake. Linoleic acid (LA) is an essential fatty acid and the major ω-6 polyunsaturated fatty acid in occidental diets, which is able to induce inappropriate inflammatory responses that contribute to several chronic diseases including cancer. In breast cancer cells, LA induces migration. However, the signal transduction pathways that mediate migration and whether LA induces invasion in MDA-MB-231 breast cancer cells have not been studied in detail. We demonstrate here that LA induces Akt2 activation, invasion, an increase in NFκB-DNA binding activity, miR34a upregulation and miR9 downregulation in MDA-MB-231 cells. Moreover, Akt2 activation requires EGFR and PI3K activity, whereas migration and invasion are dependent on FFAR4, EGFR and PI3K/Akt activity. Our findings demonstrate, for the first time, that LA induces migration and invasion through an EGFR-/PI3K-/Akt-dependent pathway in MDA-MB-231 breast cancer cells.

Extracellular vesicles from women with breast cancer promote an epithelial-mesenchymal transition-like process in mammary epithelial cells MCF10A.

Extracellular vesicles (EVs) mediate many stages of tumor progression including angiogenesis, escape from immune surveillance, and extracellular matrix degradation. We studied whether EVs from plasma of women with breast cancer are able to induce an epithelial-mesenchymal transition (EMT) process in mammary epithelial cells MCF10A. Our findings demonstrate that EVs from plasma of breast cancer patients induce a downregulation of E-cadherin expression and an increase of vimentin and N-cadherin expression. Moreover, EVs induce migration and invasion, as well as an increase of NFκB-DNA binding activity and MMP-2 and MMP-9 secretions. In summary, our findings demonstrate, for the first time, that EVs from breast cancer patients induce an EMT-like process in human mammary non-tumorigenic epithelial cells MCF10A.