RESUMO
BACKGROUND: Very recently, it has been reported that exposure to different mixtures of organochlorine pesticides (OCP) is associated with the development of diabetes mellitus (DM). In Mexico, DM is a public health problem that might be related to the historical intense use of OCP. We aimed to evaluate, the association between DM and serum concentrations of OCP mixtures, and identify the main contributors within them. METHODS: We conducted a secondary cross-sectional analysis on the control group from a breast cancer population-based case-control study conducted from 2007 to 2011 in Northern Mexico. We identified 214 self-reported diabetic women and 694 non-diabetics. We obtained direct information about sociodemographic, lifestyle and reproductive characteristics. We determined 24 OCP and metabolites in serum by gas chromatography using an electron capture micro detector. We used Weighted Quantile Sum regression to assess the association of DM and exposure to multiple OCP, and the contribution of each compound within the mixture. RESULTS: We found a positive adjusted association between DM and an OCP mixture (OR: 2.63, 95%CI: 1.85, 3.74), whose primary contribution arose from p, p'-DDE (mean weight 23.3%), HCB (mean weight 17.3%), trans nonachlor (mean weight 15.4%), o, p'-DDE (mean weight 7.3%), heptachlor epoxide (mean weight 5.9%), oxychlordane (mean weight 4.7%), and heptachlor (mean weight 4.5%). In addition, these OCP along with p, p'-DDT and cis chlordane, were of concern and remained associated when excluding hypertensive women from the analysis (OR 2.55; 95% CI 1.56, 4.18). CONCLUSIONS: Our results indicate, for the first time in a Latin-American population, that the concomitant exposure to multiple OCP is associated with DM. Further research is needed since the composition of OCP mixtures may vary according to regional pesticides use patterns.
Assuntos
Exposição Ambiental , Poluentes Ambientais , Hidrocarbonetos Clorados , Praguicidas , Humanos , Hidrocarbonetos Clorados/sangue , Feminino , México/epidemiologia , Praguicidas/sangue , Pessoa de Meia-Idade , Estudos Transversais , Estudos de Casos e Controles , Adulto , Poluentes Ambientais/sangue , Exposição Ambiental/análise , Exposição Ambiental/efeitos adversos , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/sangue , IdosoRESUMO
The advent of immune checkpoint inhibitors (ICIs) has represented a breakthrough in the treatment of many cancers, although a high number of patients fail to respond to ICIs, which is partially due to the ability of tumor cells to evade immune system surveillance. Non-coding microRNAs (miRNAs) have been shown to modulate the immune evasion of tumor cells, and there is thus growing interest in elucidating whether these miRNAs could be targetable or proposed as novel biomarkers for prognosis and treatment response to ICIs. We therefore performed an extensive literature analysis to evaluate the clinical utility of miRNAs with a confirmed direct relationship with treatment response to ICIs. As a result of this systematic review, we have stratified the miRNA landscape into (i) miRNAs whose levels directly modulate response to ICIs, (ii) miRNAs whose expression is modulated by ICIs, and (iii) miRNAs that directly elicit toxic effects or participate in immune-related adverse events (irAEs) caused by ICIs.
Assuntos
Inibidores de Checkpoint Imunológico , MicroRNAs , Neoplasias , Humanos , MicroRNAs/genética , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias/genética , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Biomarcadores Tumorais/genéticaRESUMO
This study aimed to estimate the carcinogenic and non-carcinogenic risk as well as the attributable cases due to exposure to organochlorine pesticides (OCPs): hexachlorobenzene (HCB), dichlorophenyltrichloroethane (DDT), hexachlorocyclohexane (HCH), heptachlor, and chlordane. From serum concentrations of pesticides of interest in a sample of 908 women from Northern Mexico, the risk for both cancer and non-cancer health effects was evaluated. The population attributable fraction (PAF) was also calculated based on summary association estimates between exposure to OCPs and different health events. Findings revealed that due to their OCP exposure slightly less than half of the women in the sample were at increased risk of developing non-cancerous diseases. Moreover, approximately 25% and 75% of participants were at risk of develop some type of cancer associated with their HCB and DDE concentrations, respectively. In addition, it was estimated that 40.5% of type 2 diabetes, 18.7% of endometriosis, and 23.1% of non-Hodgkin's lymphoma cases could have been prevented if women had not been exposed to these OCPs. Results suggest that the use of OCPs may have contributed to the disease burden in the study area and, based on the time required for these substances to be eliminated from the body, there are probably some women who are still at elevated risk of developing diseases associated to OCPs.
Assuntos
Diabetes Mellitus Tipo 2 , Hidrocarbonetos Clorados , Neoplasias , Praguicidas , Humanos , Feminino , Hexaclorobenzeno/análise , Carcinógenos , México/epidemiologia , Monitoramento Ambiental , Praguicidas/análise , Hidrocarbonetos Clorados/análise , Neoplasias/induzido quimicamente , Neoplasias/epidemiologiaRESUMO
Humans are environmentally exposed to many metals throughout their lives. Simultaneous exposure to several metals could result in synergistic or antagonistic toxicological effects among them; however, the information on exposure to mixtures of metals and breast cancer (BC) is scarce. The objective of this report was to compare metals considered human carcinogens, individually and as mixtures, in women with and without BC. This is a secondary analysis of a population-based case-control study that was carried out from 2007 to 2011 in Northern Mexico. A total of 499 histologically confirmed BC cases and 499 controls were included. Information about sociodemographic, lifestyle and reproductive characteristics was obtained by in-person interviews. Urinary concentrations of aluminum (Al), cadmium (Cd), chromium (Cr), nickel (Ni), lead (Pb), antimony (Sb), cobalt (Co), molybdenum (Mo), tin (Sn), and vanadium (V) were determined by inductively coupled plasma triple quadrupole. Metal mixtures were identified by principal component analysis with creatinine-corrected metals. Over 90% of subjects had metal measurements above the detection limit except tin (86%) and antimony (78.4%). After adjusting by selected covariables, we observed that the individual urinary concentrations of V, Co, and Mo were lower among cases compared to controls; in contrast to Sn that had higher concentrations. We identified two principal component mixtures with opposite relationships with BC: Cr, Ni, Sb, Al, Pb and Sn (OR = 1.15; CI95% 1.06,1.25) and Mo and Co (OR = 0.56; CI95% 0.49,0.64). This is the first study that identified urinary metal mixtures that differed between women with and without BC. Our results warrant confirmation in further prospective epidemiological studies. In addition, the elucidation of underlying mechanisms of metal interactions on BC risk deserves further research.
Assuntos
Neoplasias da Mama , Metais Pesados , Alumínio/análise , Antimônio , Neoplasias da Mama/epidemiologia , Estudos de Casos e Controles , Cromo/análise , Cobalto , Feminino , Humanos , Chumbo/análise , Metais Pesados/análise , México/epidemiologia , Molibdênio , Níquel , Estanho/análiseRESUMO
The placebo effect can be defined as the improvement of symptoms in a patient after the administration of an innocuous substance in a context that induces expectations regarding its effects. During recent years, it has been discovered that the placebo response not only has neurobiological functions on analgesia, but that it is also capable of generating effects on the immune and endocrine systems. The possible integration of changes in different systems of the organism could favor the well-being of the individuals and go hand in hand with conventional treatment for multiple diseases. In this sense, classic conditioning and setting expectations stand out as psychological mechanisms implicated in the placebo effect. Recent advances in neuroimaging studies suggest a relationship between the placebo response and the opioid, cannabinoid, and monoaminergic systems. Likewise, a possible immune response conditioned by the placebo effect has been reported. There is evidence of immune suppression conditioned through the insular cortex and the amygdala, with noradrenalin as the responsible neurotransmitter. Finally, a conditioned response in the secretion of different hormones has been determined in different studies; however, the molecular mechanisms involved are not entirely known. Beyond studies about its mechanism of action, the placebo effect has proved to be useful in the clinical setting with promising results in the management of neurological, psychiatric, and immunologic disorders. However, more research is needed to better characterize its potential use. This review integrates current knowledge about the psycho-neuro-endocrine-immune basis of the placebo effect and its possible clinical applications.
Assuntos
Analgesia , Efeito Placebo , Sistema Endócrino , Humanos , Dor/tratamento farmacológico , Manejo da DorRESUMO
Electroconvulsive therapy (ECT) is based on conducting an electrical current through the brain to stimulate it and trigger generalized convulsion activity with therapeutic ends. Due to the efficient use of ECT during the last years, interest in the molecular bases involved in its mechanism of action has increased. Therefore, different hypotheses have emerged. In this context, the goal of this review is to describe the neurobiological, endocrine, and immune mechanisms involved in ECT and to detail its clinical efficacy in different psychiatric pathologies. This is a narrative review in which an extensive literature search was performed on the Scopus, Embase, PubMed, ISI Web of Science, and Google Scholar databases from inception to February 2022. The terms "electroconvulsive therapy", "neurobiological effects of electroconvulsive therapy", "molecular mechanisms in electroconvulsive therapy", and "psychiatric disorders" were among the keywords used in the search. The mechanisms of action of ECT include neurobiological function modifications and endocrine and immune changes that take place after ECT. Among these, the decrease in neural network hyperconnectivity, neuroinflammation reduction, neurogenesis promotion, modulation of different monoaminergic systems, and hypothalamus-hypophysis-adrenal and hypothalamus-hypophysis-thyroid axes normalization have been described. The majority of these elements are physiopathological components and therapeutic targets in different mental illnesses. Likewise, the use of ECT has recently expanded, with evidence of its use for other pathologies, such as Parkinson's disease psychosis, malignant neuroleptic syndrome, post-traumatic stress disorder, and obsessive-compulsive disorder. In conclusion, there is sufficient evidence to support the efficacy of ECT in the treatment of different psychiatric disorders, potentially through immune, endocrine, and neurobiological systems.
Assuntos
Eletroconvulsoterapia , Transtorno Obsessivo-Compulsivo , Transtornos Psicóticos , Humanos , Sistemas Neurossecretores , Transtornos Psicóticos/psicologia , Resultado do TratamentoRESUMO
We evaluated the association between dietary patterns and breast cancer (BC) subtypes among women from Northern Mexico. From a study of incident cases and population controls that was carried out from 2007 to 2011, a subsample of 509 cases matched 1:1 by age with 509 controls was selected. Information about expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) was available from medical records to classify BC on luminal (ER + and/or PR+/HER2-), HER2+ (ER+/- and/or PR+/-/HER2+), or triple negative (ER- and PR-/HER2-). Dietary information was gathered using a semiquantitative food frequency questionnaire and a factor analysis was used to obtain dietary patterns. The association between each dietary pattern and BC molecular subtypes was assessed through conditional logistic regression models. Two dietary patterns were identified. The first (mainly characterized by meat, high fat, and sugary cereals) was positively associated with BC (odds ratio, OR = 12.62; 95% CI: 7.42, 21.45); the second (consisting of corn, legumes, and other vegetables) was inversely associated with BC (OR = 0.50; 95% CI: 0.40, 0.62). Both associations remained significant by BC molecular subtypes. These findings could contribute to the development of public health strategies for BC prevention.
Assuntos
Neoplasias da Mama , Biomarcadores Tumorais , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Neoplasias da Mama/metabolismo , Feminino , Humanos , Modelos Logísticos , México/epidemiologia , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismoRESUMO
OBJECTIVE: To evaluate the association between BC and urinary concentrations of free-bisphenol A (BPA-F), the biological form of BPA, among women residing in Northern Mexico. METHODS: The population under study comprised 394 histologically confirmed BC cases and 404 age-matched controls. Women were interviewed face to face about their sociodemographic and reproductive characteristics. BPA-F was determined by high-pressure liquid chromatography equipped with a fluorescence detector (HPLC/FLD). Logistic regression models were used to estimate the adjusted BC risk in relation to BPA-F. RESULTS: BPA-F geometric mean was significantly higher among cases compared to controls (3.16 µg/L in cases and 2.47 µg/L in controls). A significant adjusted BC odds ratio of 2.31 (95% CI: 1.43-3.74) was estimated for the highest category of BPA-F compared to the lowest category. CONCLUSION: BPA-F may be an environmental cofactor of BC. Since this is the first report on BPA-F association with BC, our results need to be replicated.
Assuntos
Compostos Benzidrílicos/efeitos adversos , Neoplasias da Mama/induzido quimicamente , Exposição Ambiental/efeitos adversos , Fenóis/efeitos adversos , Adolescente , Adulto , Idoso , Compostos Benzidrílicos/urina , Neoplasias da Mama/epidemiologia , Estudos de Casos e Controles , Exposição Ambiental/análise , Feminino , Humanos , Entrevistas como Assunto , México/epidemiologia , Pessoa de Meia-Idade , Fenóis/urina , Adulto JovemRESUMO
The yes-associated protein (YAP) and the transcriptional coactivator with PDZ-binding motif (TAZ) are transcriptional coactivators, members of the Hippo signaling pathway, which play a critical role in cell growth regulation, embryonic development, regeneration, proliferation, and cancer origin and progression. The mechanism involves the nuclear binding of the un-phosphorylated YAP/TAZ complex to release the transcriptional enhanced associate domain (TEAD) from its repressors. The active ternary complex is responsible for the aforementioned biological effects. Overexpression of YAP/TAZ has been reported in cancer stem cells and tumor resistance. The resistance involves chemotherapy, targeted therapy, and immunotherapy. This review provides an overview of YAP/TAZ pathways' role in carcinogenesis and tumor microenvironment. Potential therapeutic alternatives are also discussed.
Assuntos
Carcinogênese/metabolismo , Carcinogênese/patologia , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional/metabolismo , Microambiente Tumoral , Proteínas de Sinalização YAP , Animais , Resistencia a Medicamentos Antineoplásicos , Humanos , Mecanotransdução CelularRESUMO
Chronic pain (CP) is a severe clinical entity with devastating physical and emotional consequences for patients, which can occur in a myriad of diseases. Often, conventional treatment approaches appear to be insufficient for its management. Moreover, considering the adverse effects of traditional analgesic treatments, specialized pro-resolving lipid mediators (SPMs) have emerged as a promising alternative for CP. These include various bioactive molecules such as resolvins, maresins, and protectins, derived from ω-3 polyunsaturated fatty acids (PUFAs); and lipoxins, produced from ω-6 PUFAs. Indeed, SPMs have been demonstrated to play a central role in the regulation and resolution of the inflammation associated with CP. Furthermore, these molecules can modulate neuroinflammation and thus inhibit central and peripheral sensitizations, as well as long-term potentiation, via immunomodulation and regulation of nociceptor activity and neuronal pathways. In this context, preclinical and clinical studies have evidenced that the use of SPMs is beneficial in CP-related disorders, including rheumatic diseases, migraine, neuropathies, and others. This review integrates current preclinical and clinical knowledge on the role of SPMs as a potential therapeutic tool for the management of patients with CP.
Assuntos
Dor Crônica/metabolismo , Dor Crônica/terapia , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-6/metabolismo , Mediadores da Inflamação/metabolismo , Manejo da Dor , Animais , HumanosRESUMO
Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver disorder, affecting around 25% of the population worldwide. It is a complex disease spectrum, closely linked with other conditions such as obesity, insulin resistance, type 2 diabetes mellitus, and metabolic syndrome, which may increase liver-related mortality. In light of this, numerous efforts have been carried out in recent years in order to clarify its pathogenesis and create new prevention strategies. Currently, the essential role of environmental pollutants in NAFLD development is recognized. Particularly, endocrine-disrupting chemicals (EDCs) have a notable influence. EDCs can be classified as natural (phytoestrogens, genistein, and coumestrol) or synthetic, and the latter ones can be further subdivided into industrial (dioxins, polychlorinated biphenyls, and alkylphenols), agricultural (pesticides, insecticides, herbicides, and fungicides), residential (phthalates, polybrominated biphenyls, and bisphenol A), and pharmaceutical (parabens). Several experimental models have proposed a mechanism involving this group of substances with the disruption of hepatic metabolism, which promotes NAFLD. These include an imbalance between lipid influx/efflux in the liver, mitochondrial dysfunction, liver inflammation, and epigenetic reprogramming. It can be concluded that exposure to EDCs might play a crucial role in NAFLD initiation and evolution. However, further investigations supporting these effects in humans are required.
Assuntos
Disruptores Endócrinos/toxicidade , Poluentes Ambientais/toxicidade , Metabolismo dos Lipídeos/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Compostos Benzidrílicos/toxicidade , Cumestrol/toxicidade , Dioxinas/toxicidade , Disruptores Endócrinos/classificação , Genisteína/toxicidade , Humanos , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/patologia , Fenóis/toxicidade , Fitoestrógenos/toxicidade , Bifenilos Policlorados/toxicidadeRESUMO
The actin cytoskeleton coordinates the organization of signaling microclusters at the immune synapse (IS); however, the mechanisms involved remain poorly understood. We show here that nitric oxide (NO) generated by endothelial nitric oxide synthase (eNOS) controls the coalescence of protein kinase C-θ (PKC-θ) at the central supramolecular activation cluster (c-SMAC) of the IS. eNOS translocated with the Golgi to the IS and partially colocalized with F-actin around the c-SMAC. This resulted in reduced actin polymerization and centripetal retrograde flow of ß-actin and PKC-θ from the lamellipodium-like distal (d)-SMAC, promoting PKC-θ activation. Furthermore, eNOS-derived NO S-nitrosylated ß-actin on Cys374 and impaired actin binding to profilin-1 (PFN1), as confirmed with the transnitrosylating agent S-nitroso-L-cysteine (Cys-NO). The importance of NO and the formation of PFN1-actin complexes on the regulation of PKC-θ was corroborated by overexpression of PFN1- and actin-binding defective mutants of ß-actin (C374S) and PFN1 (H119E), respectively, which reduced the coalescence of PKC-θ at the c-SMAC. These findings unveil a novel NO-dependent mechanism by which the actin cytoskeleton controls the organization and activation of signaling microclusters at the IS.
Assuntos
Actinas/metabolismo , Sinapses Imunológicas/enzimologia , Isoenzimas/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Profilinas/metabolismo , Proteína Quinase C/metabolismo , Processamento de Proteína Pós-Traducional , Linfócitos T/metabolismo , Substituição de Aminoácidos , Linhagem Celular , Células Cultivadas , Cisteína/metabolismo , Ativação Enzimática , Complexo de Golgi/enzimologia , Complexo de Golgi/imunologia , Complexo de Golgi/metabolismo , Humanos , Sinapses Imunológicas/imunologia , Sinapses Imunológicas/metabolismo , Isoenzimas/química , Isoenzimas/genética , Proteínas Luminescentes/antagonistas & inibidores , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Mutação , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Óxido Nítrico Sintase Tipo III/genética , Profilinas/genética , Proteína Quinase C/química , Proteína Quinase C/genética , Proteína Quinase C-theta , Transporte Proteico , Pseudópodes , Interferência de RNA , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Linfócitos T/citologia , Linfócitos T/imunologiaRESUMO
The objective was to estimate the risk of breast cancer (BC) molecular subtypes in relation to the average glycemic index (GI) and the dietary glycemic load (GL) in Mexican women. From 2007 to 2011, a study of incident cases and population controls was conducted in five states of northern Mexico. A subsample of 509 cases matched 1:1 by age with 509 controls was selected. With a food frequency questionnaire, information about diet was obtained, and GI and GL were calculated. The expression of human epidermal growth factor receptor 2 (HER2), and estrogen (ER) and progesterone (PR) receptors in tumors was obtained from medical records. Patients were classified as luminal A (RE+ and/or PR+/HER2-), HER2+ (RE+ and/or PR+/HER2+ and RE-/PR-/HER2+), or triple negative (TN) (RE-/PR-/HER2-). GI and GL associations with BC molecular subtypes were evaluated using conditional logistic regression models. GI was positively associated with luminal A (OR= 1.12; 95% CI: 1.03, 1.22), HER2+ (OR= 1.15; 95% CI: 1.02, 1.30), and TN (OR= 1.20; 95% CI: 1.03, 1.39) BC. GL was not associated with BC molecular subtypes. These results suggest that the type of carbohydrate consumed is associated with increased BC regardless of the luminal A, HER2+, and TN subtypes.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/etiologia , Dieta/efeitos adversos , Índice Glicêmico , Carga Glicêmica , Adulto , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Humanos , México , Pessoa de Meia-Idade , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos RetrospectivosRESUMO
BACKGROUND: Child neurodevelopment has been positively linked to maternal intake of polyunsaturated fatty acids (PUFAs) during pregnancy; however, it is unknown if that relationship persists among populations exposed to environmental neurotoxicants. OBJECTIVE: The aim of this work was to assess whether maternal dietary intake of PUFAs during pregnancy is positively associated with child neurodevelopment, whose mothers were environmentally exposed to 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT). METHODS: A prospective cohort study with 276 mother-child pairs was performed in Mexico. Neurodevelopment was assessed by Bayley Scales II from children age 1 to 30 months. Dietary PUFAs intake was estimated by Food Frequency Questionnaire at 1st and 3rd trimester of pregnancy. DDE (1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene, the main metabolite of DDT) maternal serum levels were determined by electron capture gas chromatography. Longitudinal multivariate linear mixed-effects analysis, which combines mental (MDI) and motor (PDI) Bayley scales in a single model, were performed. RESULTS: Our results show that in a sample environmentally exposed to DDT, maternal ingestion of DPA during the first trimester of pregnancy was positively associated with MDI (ß = 0.10, 95% CI 0.02, 0.18) in children from 1 to 30 months. Likewise, our results suggest that dietary ALA may be also related to MDI. CONCLUSION: DPA may benefit neurodevelopment even in populations exposed to DDT. Our results strengthen the importance of PUFAs intake during the prenatal period.
Assuntos
Desenvolvimento Infantil/efeitos dos fármacos , DDT , Poluentes Ambientais , Ácidos Graxos Insaturados/administração & dosagem , Inseticidas , Exposição Materna , Pré-Escolar , Estudos de Coortes , Dieta , Feminino , Humanos , Lactente , Recém-Nascido , Troca Materno-Fetal , México , Mães , GravidezRESUMO
Bisphenol A (BPA), found in plastics and epoxy resins, is one of the most studied chemicals. BPA is regarded as an endocrine disruptor and has been related to adverse health effects in humans. However, some regulatory agencies around the world have concluded that BPA is safe at current human exposure levels. As the scientific community attempts to settle the debate on BPA's health effects, regulatory agencies have been put into a challenging public health policy situation. The United States has implemented no regulatory actions due to safety concerns, while Europe has used the precautionary principle to guide its regulation in the face of scientific uncertainty. In this paper, we explore the debate surrounding BPA regulation and the possibility for countries to introduce guidelines, using Mexico as an example. Policy change determinants analysis suggest that countries can and should impose regulations on BPA.
El bisfenol A (BPA), presente en plásticos y resinas epoxi, es uno de los químicos más estudiados. Se considera un disruptor endocrino y se ha relacionado con efectos adversos para la salud humana. Algunas agencias regulatorias en el mundo han concluido que el BPA es seguro a los niveles de exposición humana actuales. Mientas la comunidad científica intenta resolver el debate sobre dichos efectos, las agencias regulatorias enfrentan una difícil situación de política pública. Los Estados Unidos de América no han implementado acciones reglamentarias por razones precautorias, mientras que Europa ha utilizado el principio precautorio para guiar su regulación ante la incertidumbre científica. En este documento exploramos el debate que rodea la regulación del BPA y la posibilidad de que los países introduzcan directrices, usando a México como ejemplo. El análisis de los determinantes del cambio de políticas sugiere que los países pueden y deben regular el BPA.
Assuntos
Compostos Benzidrílicos , Disruptores Endócrinos , Exposição Ambiental/efeitos adversos , Legislação de Medicamentos , Fenóis , Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Europa (Continente) , Humanos , México , Fenóis/toxicidade , Política Pública/legislação & jurisprudência , Estados UnidosRESUMO
Metastatic spread, not primary tumors, is the leading cause of cancer death. Glutathione (γ-glutamyl-cysteinyl-glycine, GSH) is particularly relevant in cancer cells as it is involved in regulating carcinogenic mechanisms, growth and dissemination, and multidrug and radiation resistance. Upon interaction of metastatic cells with the vascular endothelium, a high percentage of metastatic cells with high GSH levels survive the combined nitrosative and oxidative stresses elicited by the vascular endothelium. GSH release from different organs, mainly the liver, and its interorgan transport through the blood circulation to metastatic foci, promote their growth. This review focuses on the relationship among GSH and different key mechanisms that facilitate metastatic cell survival and growth, i.e. adaptive responses to stress, cell death evasion and utilization of physiological neuroendocrine mechanisms. Different strategies that are aimed at sensitizing metastases to cancer therapy by depleting metastatic cell GSH are analyzed.
Assuntos
Glutationa , Metástase Neoplásica , Neoplasias , Animais , Glutationa/metabolismo , Glutationa/fisiologia , Humanos , Camundongos , Neoplasias/metabolismo , Neoplasias/fisiopatologiaRESUMO
One of the earliest neuropathological events in Alzheimer's disease is accumulation of astrocytes at sites of Aß1-42 depositions. Our results indicate that Aß1-42 toxic peptide increases lipid peroxidation, apoptosis and cell death in neurons but not in astrocytes in primary culture. Aß1-42-induced deleterious neuronal effects are not present when neurons and astrocytes are mixed cultured. Stimulation of astrocytes with toxic Aß1-42 peptide increased p-65 and decreased IκB resulting in inflammatory process. In astrocytes Aß1-42 decreases protein expressions of sirtuin 1 (SIRT-1) and peroxisome proliferator-activated receptor γ (PPAR-γ) and over-expresses peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1) and mitochondrial transcription factor A (TFAM), protecting mitochondria against Aß1-42-induced damage and promoting mitochondrial biogenesis. In summary our data suggest that astrocytes may have a key role in protecting neurons, increasing neural viability and mitochondrial biogenesis, acquiring better oxidative stress protection and perhaps modulating inflammatory processes against Aß1-42 toxic peptide. This might be a sign of a complex epigenetic process in Alzheimer's disease development.
Assuntos
Peptídeos beta-Amiloides/toxicidade , Astrócitos/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Fragmentos de Peptídeos/toxicidade , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/farmacologia , Animais , Astrócitos/citologia , Caspase 3/metabolismo , Morte Celular/efeitos dos fármacos , Células Cultivadas , Técnicas de Cocultura , Peroxidação de Lipídeos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neurônios/efeitos dos fármacos , PPAR gama/metabolismo , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/farmacologia , Peróxidos/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Ratos , Sirtuína 1/metabolismo , Superóxido Dismutase/metabolismo , Fator de Transcrição RelA/metabolismo , Fatores de Transcrição/metabolismoRESUMO
Epidemiological studies on associations between breast cancer (BC) and organochlorine pesticides (OCP) are inconclusive. The majority of studies have evaluated the effect of single compounds without considering multiple OCP exposures and immunophenotypes of BC. We aimed to evaluate the association between BC immunophenotypes and serum OCP mixtures, and identify the main contributors within mixtures. We included 767 histopathologically confirmed incident BC cases and 908 controls from a population-based case-control study conducted from 2007 to 2011 in Northern Mexico. We obtained direct information about sociodemographic, lifestyle and reproductive characteristics. We collected data from clinical records about hormonal receptors (HR) and epidermal growth factor receptor 2 (HER2) expressions. Immunophenotypes were determined as HR+/HER2-, HER2+ or HR-/HER2-. We quantified OCP and metabolites by gas chromatography using an electron capture micro detector. We used Weighted Quantile Sum regression to assess the association of BC and exposure to multiple OCP, and their contribution within the mixture. We found a positive adjusted association between BC and an OCP mixture (OR: 3.48, 95%CI: 2.58, 4.69), whose primary contribution arose from the isomers of hexachlorocyclohexane and endosulfan, as well as endosulfan sulfate. We also identified a mixture negatively associated (OR: 0.13, 95%CI: 0.08, 0.20), characterized by p,p'-DDT and chlordane metabolites. All these associations remained regardless BC immunophenotypes. This is the first epidemiological report that identified serum OCP mixtures associated with BC immunophenotypes. Due to OCP ubiquity, biomagnification, and continuous exposure, they constitute a global problem of persistent exposure that might be related to BC risk.
Assuntos
Neoplasias da Mama , Hidrocarbonetos Clorados , Praguicidas , Humanos , Hidrocarbonetos Clorados/sangue , Feminino , Praguicidas/sangue , México , Pessoa de Meia-Idade , Estudos de Casos e Controles , Adulto , Exposição Ambiental/estatística & dados numéricos , Imunofenotipagem , Poluentes Ambientais/sangue , Idoso , DDT/sangueRESUMO
This study aimed to assess the post-harvest dynamics of seedless conical and mini-conical pepper cultivars in terms of fruit weight loss, dry matter content, and soluble solid content. The above parameters were demonstrated to be effective commercial pepper shelf-life indicators. The commercial quality of pepper fruit intended for export was evaluated weekly under simulated fruit storage conditions for over 28 d. Results revealed that fruit weight loss, dry matter content, and soluble solid content were affected by cultivar type and storage duration. Additionally, a strong correlation between these variables was observed confirming their linear relationship which was more profound between dry matter and total soluble solid content. Daily changes during storage were similar in both seedless conical and mini-conical peppers, while the fruit weight loss daily rate was greater than that of dry matter. Water loss was identified to be the main factor causing reduced fruit quality. Solid content reduction occurred predominately during the initial storage period. Notably, fruit with lower dry matter content at harvest tended to maintain their commercial quality for a longer time due to their ability to resist water loss without any visible signs of deterioration, which is beneficial during prolonged storage.
RESUMO
OBJECTIVE: We aimed to evaluate the association between food groups and mixtures of urinary metal concentrations in a sample of women; as well as identify the most important metals within each mixture. METHODS: This is a cross-sectional analysis between food groups consumption and mixtures of various metals in urine from 439 women, ≥18 years old, from Northen Mexico. We estimated the dietary intake of 20 food groups through a validated semi-quantitative food frequency questionnaire. Urinary metal concentration of aluminum, antimony, arsenic, barium, cadmium, cesium, chromium, cobalt, copper, lead, manganese, magnesium, molybdenum, nickel, selenium, thallium, tin, vanadium, and zinc, were measured by inductively coupled plasma triple quad. We used weighted quantile sum (WQS) regression with binomial family specification to assess the association of food groups and metal mixtures, as well as to identify the most important ones. RESULTS: We identified tin, lead, and antimony as the most important metals, in the metal mixtures that were positively associated with the consumption of eggs, non-starchy vegetables, fruits, seafood, corn, oil seeds, chicken, soda, legumes, red and/or processed meats, as well as negatively with the consumption of alliums, corn tortillas and/or vegetable oils. CONCLUSION: Our findings suggest that food consumption is related to more than one metal in the study sample, and highlights the presence of some of them. Further research is required to identify the possible sources of metals in food, as well as the chronic adverse health effects attributed to their simultaneous presence.