Development of a Nanostructured Electrochemical Genosensor for the Detection of the K-ras Gene.

In the scientific literature, it has been documented that electrochemical genosensors are novel analytical tools with proven clinical diagnostic potential for the identification of carcinogenic processes due to genetic and epigenetic alterations, as well as infectious diseases due to viruses or bacteria. In the present work, we describe the construction of an electrochemical genosensor for the identification of the k12p.1 mutation; it was based on use of Screen-Printed Gold Electrode (SPGE), Cyclic Voltammetry (CV), and Atomic Force Microscopy (AFM), for the monitoring the electron transfer trough the functionalized nanostructured surface and corresponding morphological changes. The sensitivity of the genosensor showed a linear response for the identification of the k12p.1 mutation of the K-ras gene in the concentration range of 10 fM to 1 µM with a detection limit of 7.96 fM in the presence of doxorubicin (Dox) as DNA intercalating agent and indicator of the hybridization reaction. Thus, the electrochemical genosensor developed could be useful for the identification of diseases related with the K-ras oncogene.

Garlic (Allium sativum L.): A Brief Review of Its Antigenotoxic Effects.

Traditional Medicine/Complementary and Alternative Medicine is a practice that incorporates medicine based on plants, animals, and minerals for diagnosing, treating, and preventing certain diseases, including chronic degenerative diseases such as obesity, diabetes, hypertension, atherosclerosis, and cancer. Different factors generate its continued acceptance, highlighting its diversity, easy access, low cost, and the presence of relatively few adverse effects and, importantly, a high possibility of discovering antigenotoxic agents. In this regard, it is known that the use of different antigenotoxic agents is an efficient alternative to preventing human cancer and that, in general, these can act by means of a combination of various mechanisms of action and against one or various mutagens and/or carcinogens. Therefore, it is relevant to confirm its usefulness, efficacy, and its spectrum of action through different assays. With this in mind, the present manuscript has as its objective the compilation of different investigations carried out with garlic that have demonstrated its genoprotective capacity, and that have been evaluated by means of five of the most outstanding tests (Ames test, sister chromatid exchange, chromosomal aberrations, micronucleus, and comet assay). Thus, we intend to provide information and bibliographic support to investigators in order for them to broaden their studies on the antigenotoxic spectrum of action of this perennial plant.

Evidence of Some Natural Products with Antigenotoxic Effects. Part 2: Plants, Vegetables, and Natural Resin.

Cancer is one of the leading causes of death worldwide. The agents capable of causing damage to genetic material are known as genotoxins and, according to their mode of action, are classified into mutagens, carcinogens, or teratogens. Genotoxins are also involved in the pathogenesis of several chronic degenerative diseases, including hepatic, neurodegenerative, and cardiovascular disorders; diabetes; arthritis; cancer; chronic inflammation; and ageing. In recent decades, researchers have found novel bioactive phytocompounds able to counteract the effects of physical and chemical mutagens. Several studies have shown the antigenotoxic potential of different fruits and plants (Part 1). In this review (Part 2), we present a research overview conducted on some plants and vegetables (spirulina, broccoli, chamomile, cocoa, ginger, laurel, marigold, roselle, and rosemary), which are frequently consumed by humans. In addition, an analysis of some phytochemicals extracted from those vegetables and the analysis of a resin (propolis),whose antigenotoxic power has been demonstrated in various tests, including the Ames assay, sister chromatid exchange, chromosomal aberrations, micronucleus, and comet assay, was also performed.

Molecular recognition between potential natural inhibitors of the Keap1-Nrf2 complex.

Disrupting the Keap1-Nrf2 pathway enhances Nrf2 activity, which has been identified as an important approach for the prevention of different chronic diseases in which oxidative stress and inflammation are present, such as cancer, diabetes, Alzheimer's and Parkinson's. Based on the high potential to modulate antioxidant, anti-inflammatory and anticancer properties that the discovery of Keap1-Nrf2 protein-protein interaction inhibitors would represent, the utilization of some natural compounds has emerged as a promising strategy to identify new drugs. To gain insight into the structural and energetic basis of the molecular recognition between some natural inhibitors that could work as inhibitors of the Keap1-Nrf2 complex, we evaluated the binding properties between four natural compounds present in the extract of Geranium schiedeanum (Gs): 3-O-a-L arabinofuranoside-7-O-a-l-rhamnopyranoside of kaempferol (KAM), gallic acid (GAL), ellagic acid (ELL) and geranium acetonitrile (ACE), which based on experimental findings have been proposed as possible Keap1-Nrf2 PPI inhibitors. Computational studies combining docking and MD simulations accompanied by the MMGBSA approach revealed that KAM and ACE directly interact with residues in the Kelch domain that participate in the molecular recognition of Nrf2, indicating that both natural compounds could act as activators of Nrf2, whereas GAL and ELL are possible free radical scavengers.

Evidence of Some Natural Products with Antigenotoxic Effects. Part 1: Fruits and Polysaccharides.

Cancer is one of the leading causes of deaths worldwide. The agents capable of causing damage to genetic material are known  as genotoxins and, according to their mode of action, are classified into mutagens, carcinogens or teratogens. Genotoxins are  involved in the pathogenesis of several chronic degenerative diseases including hepatic, neurodegenerative and cardiovascular  disorders, diabetes, arthritis, cancer, chronic inflammation and ageing. In recent decades, researchers have found novel bioactive  phytocompounds able to counteract the effects of physical and chemical mutagens. Several  studies  have  shown potential antigenotoxicity in a variety of fruits. In this review (Part 1), we present an overview of research conducted on some fruits (grapefruit, cranberries, pomegranate, guava, pineapple, and mango) which are frequentl consumed by humans, as well as  the  analysis of some phytochemicals extracted from fruits and yeasts which have demonstrated antigenotoxic capacity in various  tests, including the Ames assay, sister chromatid exchange, chromosomal aberrations, micronucleus and comet assay.

Prevention of Aflatoxin B1-Induced DNA Breaks by ß-D-Glucan.

Aflatoxins are a group of naturally-occurring carcinogens that are known to contaminate different human and animal foodstuffs. Aflatoxin B1 (AFB1) is the most genotoxic hepatocarcinogenic compound of all of the aflatoxins. In this report, we explore the capacity of ß-D-glucan (Glu) to reduce the DNA damage induced by AFB1 in mouse hepatocytes. For this purpose, we applied the comet assay to groups of animals that were first administered Glu in three doses (100, 400 and 700 mg/kg bw, respectively) and, 20 min later, 1.0 mg/kg of AFB1. Liver cells were obtained at 4, 10 and 16 h after the chemical administration and examined. The results showed no protection of the damage induced by AFB1 with the low dose of the polysaccharide, but they did reveal antigenotoxic activity exerted by the two high doses. In addition, we induced a co-crystallization between both compounds, determined their fusion points and analyzed the molecules by UV spectroscopy. The data suggested the formation of a supramolecular complex between AFB1 and ß-D-glucan.

Inhibitory Effect of Spirulina maxima on the Azoxymethane-induced Aberrant Colon Crypts and Oxidative Damage in Mice.

BACKGROUND: Spirulina maxima (Sm) is a cyanobacterium well known because of its high nutritive value, as well as its anti-inflammatory, anti-hyperlipidemic, antioxidant, and anti-genotoxic activities. OBJECTIVE: To determine the capacity of Sm to inhibit the induction of aberrant colon crypts (AC), as well as the level of lipid peroxidation and DNA oxidative damage in mice treated with azoxymethane (AOM). MATERIALS AND METHODS: Sm (100, 400, and 800 mg/kg) was daily administered to animals by the oral route during 4 weeks, while AOM (10 mg/kg) was intraperitoneally injected to mice twice in weeks 2 and 3 of the assay. We also included a control group of mice orally administered with distilled water along the assay, as well as other group orally administered with the high dose of Sm. RESULTS: A significant decrease in the number of AC with the three tested doses of Sm, with a mean protection of 51.6% respect to the damage induced by AOM. Also, with the three doses of the alga, we found a reduction in the level of lipoperoxidation, as well as in regard to the percentage of the DNA adduct 8-hydroxy-2'- deoxyguanosine. CONCLUSION: Sm possesses anti-precarcinogenic potential in vivo, as well as capacity to reduce the oxidative damage induced by AOM. SUMMARY: Azoxymethane (AOM) induced a high number of colon aberrant crypts in mouse. It also increased the level of peroxidation and of DNA oxidation in the same organ.Spirulina maxima significantly reduced the number of AOM-induced colon aberrant crypts in mouse. It also reduced the AOM-induced lipid and DNA oxidation in mouse.The results suggest a chemopreventive potential for the tested algae.

Antigenotoxic effect of Chamomilla recutita (L.) Rauschert essential oil in mouse spermatogonial cells, and determination of its antioxidant capacity in vitro.

Chamomilla recutita (L.) Rauschert (Asteraceae), popularly known as chamomile, is a plant used in traditional medicine for various therapeutic purposes. Chamomile essential oil (CEO) is particularly known to inhibit the genotoxic damage produced by mutagens in mice somatic cells. The aim of this research was to determine the inhibitory potential of CEO on the genotoxic damage produced by daunorubicin (DAU) in mice germ cells. We evaluated the effect of 5, 50, and 500 mg/kg of essential oil on the rate of sister chromatid exchange (SCE) induced in spermatogonia by 10 mg/kg of the mutagen. We found no genotoxicity of CEO, but detected an inhibition of SCE after the damage induced by DAU; from the lowest to the highest dose of CEO we found an inhibition of 47.5%, 61.9%, and 93.5%, respectively. As a possible mechanism of action, the antioxidant capacity of CEO was determined using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging method and ferric thiocyanate assays. In the first test we observed a moderate scavenging potential of the oil; nevertheless, the second assay showed an antioxidant capacity similar to that observed with vitamin E. In conclusion, we found that CEO is an efficient chemoprotective agent against the damage induced by DAU in the precursor cells of the germinal line of mice, and that its antioxidant capacity may induce this effect.

Investigation on the protective effect of α-mannan against the DNA damage induced by aflatoxin B1in mouse hepatocytes.

Aflatoxin B(1) is a contaminant of agricultural and dairy products that can be related to mutagenic and carcinogenic effects. In this report we explore the capacity of alpha-mannan (Man) to reduce the DNA damage induced by AFB(1) in mouse hepatocytes. For this purpose we applied the comet assay to groups of animals which were first administered Man (100, 400 and 700 mg/kg, respectively) and 20 min later 1.0 mg/kg of AFB(1). Liver cells were obtained at 4, 10, and 16 h after the chemical administration and examined. The results showed no protection of the damage induced by AFB(1) with the low dose of the polysaccharide, but they did reveal antigenotoxic activity exerted by the two high doses. In addition, we induced a co-crystallization between both compounds, determined their fusion points and analyzed the molecules by UV spectroscopy. The obtained data suggested the formation of a supramolecular complex between AFB(1) and Man.

Cambios en la expresión de laminina en el ligamento periodontal en dientes sujetos a tensión ortodóntica en humanos / Laminin expression changes in periodontal ligament of teeth subjected to orthodontic forces in humans

Objetivo: determinar la presencia de laminina, en el ligamento periodontal (LPD) en premolares a los que se les aplicó fuerzas ortodónticas. Hipótesis: la laminina presente en el ligamento periodontal de dientes sujetos a presión ortodóntica presentarán modificación en su expresión. Diseño, material y métodos: se colocó aparatología en sujetos clínicamente sanos en sus primeros premolares superiores, siendo el derecho experimental (sometido a fuerza ortodóncica) y el izquierdo, el control (sin aparatología). Al término de tres semanas, se obtuvieron los LPDs para determinar la presencia de laminina por medio de western blot. Resultados: en comparación con los premolares que no fueron sometidos a fuerzas ortodónticas, los que tuvieron aparatología presentaron una disminución estadísticamente significativa en la presencia de laminina. Conclusiones: nuestros resultados indican que existen cambios a nivel molecular en el LPD de dientes que fueron sometidos a fuerzas ortodónticas

El factor de crecimiento transformante-alfa (tgf-a) y el factor de crecimiento epidermoide (egf) en el síndrome de ovarios poliquísticos: posible papel en la disminución de los mecanismos apoptóticos en el folículo / Effects of transforming growth factor-alpha (TGF_alpha) y and epidermal growth factor (EGF) in polycystic ovaric syndrome on follicle apoptosis

El conocimiento en la regulación de las funciones del ovario se ha extendido del concepto clásico de la regulación endocrina por hormonas sexuales y gonadotropinas al conocimiento de regulación intraovárica, por medio de factores parácrinos y autócrinos. El crecimiento folicular y la esteroidogénesis es regulada principalmente por las gonadotropinas (hormona folículo estimulante, FSH; y la hormona luteinizante, LH) y los esteroides. Por otra parte, últimamente han aumentado las evidencias que revelan que los factores de crecimiento intraováricos juegan un papel importante en la modulación de los efectos de las gonadotropinas en las funciones del ovario.

Correlación clínico-patológico en la colecistitis crónica / Clino-pathological correlation in biliary disease

La colecistitis es un padecimiento común, que se acompaña a menudo de litiasis vesicular (85 al 90 por ciento de los pacientes). La frecuencia de litiasis aumenta con la edad y se ha relacionado con la raza, el sexo, la multiparidad, el uso de anticonceptivos hormonales y el alcoholismo. Clínicamente la colecistitis se acompaña de brotes de dolor en el hipocondrio derecho. Los datos de laboratorio no suelen ser diagnósticos por lo que la clínica continúa siendo el elemento indispensable para la identificación del padecimiento. Es un estudio prospectivo, observacional y transversal se dio seguimiento a 23 pacientes con colecistitis tratados quirúrgicamente entre el 1 de enero y el 31 de diciembre de 1996, en el Hospital de Jesús, Puebla. Se revisan los datos clínicos, los estudios de laboratorio y gabinete, así como la histopatología del hígado y vesícular biliar

El metabolismo hepático del etanol y su contribución a la enfermedad hepática / Ethanol metabolism and alcohol liver disease

El hígado es el órgano que en el humano principalmente metaboliza el etanol, pues posee tres sistemas que lo oxidan a acetaldehído que son: alcohol deshidrogenasa (ADH que se localiza en el citosol), catalasa (que se encuentran en las perixisomas), y citrocromo P-450 (que se ubica en el retículo endoplásmico liso conocido como sistema MEOS). Estos sistemas convierten al etanol en acetaldehído con la ayuda de las coenzimas NAD + y NADP +, mismas que se reducen hasta NADII y NADPII, respectivamente. El acetaldehído penetra en la mitocondría y se oxida a acetato por medio de la enzima aldehído deshidrogenasa (ALDH) y reduce una molécula de NAD + a NADH. Durante la ingestión aguda de etanol, la ADH es la principal enzima que metaboliza al etanol y participa en 85 por ciento durante la oxidación de éste, mientras que la catalasa y el sistema MEOS se encuentran inducidos y pueden llegar a metabolizar 40 por ciento del etanol ingerido. La oxidación de etanol hasta acetato produce equivalentes reductores (NADII y NADPH) en citosol y mitocondria, lo que ocasiona alteraciones en el metabolismo intermedio en los dos organitos intracelulares que, a su vez, son responsables de las alteraciones metabólicas que se encuentran el en hígado, en donde los sistemas de oxidación alternos de etanol se aumenta