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1.
Int J Mol Sci ; 25(5)2024 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-38473918

RESUMEN

The prevalence and incidence of obesity and the comorbidities linked to it are increasing worldwide. Current therapies for obesity and associated pathologies have proven to cause a broad number of adverse effects, and often, they are overpriced or not affordable for all patients. Among the alternatives currently available, natural bioactive compounds stand out. These are frequently contained in pharmaceutical presentations, nutraceutical products, supplements, or functional foods. The clinical evidence for these molecules is increasingly solid, among which epigallocatechin-3-gallate, ellagic acid, resveratrol, berberine, anthocyanins, probiotics, carotenoids, curcumin, silymarin, hydroxy citric acid, and α-lipoic acid stand out. The molecular mechanisms and signaling pathways of these molecules have been shown to interact with the endocrine, nervous, and gastroenteric systems. They can regulate the expression of multiple genes and proteins involved in starvation-satiety processes, activate the brown adipose tissue, decrease lipogenesis and inflammation, increase lipolysis, and improve insulin sensitivity. This review provides a comprehensive view of nature-based therapeutic options to address the increasing prevalence of obesity. It offers a valuable perspective for future research and subsequent clinical practice, addressing everything from the molecular, genetic, and physiological bases to the clinical study of bioactive compounds.


Asunto(s)
Antocianinas , Ácido Tióctico , Humanos , Antocianinas/uso terapéutico , Obesidad/metabolismo , Suplementos Dietéticos , Resveratrol/uso terapéutico , Ácido Tióctico/uso terapéutico
2.
Med Vet Entomol ; 37(2): 219-227, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36346249

RESUMEN

Soft ticks are neglected competent vectors of a wide range of pathogenic microorganisms, among which bacteria of the genera Rickettsia and Borrelia stand out. In Mexico, previous studies have shown the presence of a member of the Ornithodoros talaje complex in the Virginia opossum (Didelphis virginiana Didelphimorphia: Didelphidae Kerr) from southeastern Mexico. However, its specific identification has not been achieved. Two D. virginiana were treated in a private clinic during the period of April-May 2022. Tick larvae were manually removed, DNA extraction was performed, and some genes from various bacterial and parasitic pathogens were amplified and sequenced. A total of 96 larvae were recovered, which were morphologically identified as Ornithodoros puertoricensis (Ixodida: Argasidae Fox); the 16 S sequences showed a similarity of 96.79%-99.51% with sequences of O. puertoricensis from Panama and Colombia. The presence of Rickettsia felis (Rickettsiales: Rickettsiaceae Bouyer et al.) was detected in 15 specimens from one host. The soft tick O. puertoricensis is recorded for the first time as an ectoparasite of the Virginia opossum in America and represents the second report for this soft tick in Mexico since 1963. This represents the most northern record of this tick species in its geographic distribution and brings a new soft tick-Rickettsia association.


Asunto(s)
Argasidae , Ornithodoros , Rickettsia felis , Rickettsia , Animales , México , Argasidae/genética , Argasidae/microbiología , Rickettsia/genética , Larva/microbiología
3.
Molecules ; 28(24)2023 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-38138473

RESUMEN

Liver enzymes alterations (activity or quantity increase) have been recognized as biomarkers of obesity-related abnormal liver function. The intake of healthy foods can improve the activity of enzymes like aspartate and alanine aminotransferases (AST, ALT), γ-glutaminyl transferase (GGT), and alkaline phosphatase (ALP). Beans have a high concentration of several phytochemicals; however, Restriction Irrigation (RI) during plant development amends their synthesis. Using chemometric tools, we evaluated the capacity of RI-induced phytochemicals to ameliorate the high activity of liver enzymes in obese rats. The rats were induced with a high-fat diet for 4 months, subsequently fed with 20% cooked beans from well-watered plants (100/100), or from plants subjected to RI at the vegetative or reproduction stage (50/100, 100/50), or during the whole cycle (50/50) for 3 months. A partial least square discriminant analysis indicated that mostly flavonols have a significant association with serum AST and ALT activity, while isoflavones lowered GGT and ALP. For AST and ALT activity in the liver, saponins remained significant for hepatocellular protection and flavonoids remained significant as hepatobiliary protectants by lowering GGT and ALP. A principal component analysis demonstrated that several flavonoids differentiated 100/50 treatment from the rest, while some saponins were correlated to 50/100 and 50/50 treatments. The intake of beans cultivated under RI improves obesity-impaired liver alterations.


Asunto(s)
Phaseolus , Saponinas , Ratas , Animales , Quimiometría , Aspartato Aminotransferasas , Obesidad/tratamiento farmacológico , Hígado , Fosfatasa Alcalina , Alanina Transaminasa , Semillas , Flavonoides/farmacología , Fitoquímicos/farmacología
4.
Molecules ; 28(22)2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-38005322

RESUMEN

The anticarcinogenic potential of a series of 1,5-disubstituted tetrazole-1,2,3-triazole hybrids (T-THs) was evaluated in the breast cancer (BC)-derived cell lines MCF-7 (ER+, PR+, and HER2-), CAMA-1 (ER+, PR+/-, and HER2-), SKBR-3 (ER+, PR+, and HER2+), and HCC1954 (ER+, PR+, and HER2+). The T-THs 7f, 7l, and 7g inhibited the proliferation of MCF-7 and CAMA-1, HCC1954, and SKBR-3 cells, respectively. The compounds with stronger effect in terms of migration and invasion inhibition were 7o, 7b, 7n, and 7k for the CAMA-1, MCF-7, HCC1954, and SKBR-3 cells respectively. Interestingly, these T-THs were the compounds with a fluorine present in their structures. To discover a possible target protein, a molecular docking analysis was performed for p53, p38, p58, and JNK1. The T-THs presented a higher affinity for p53, followed by JNK1, p58, and lastly p38. The best-predicted affinity for p53 showed interactions between the T-THs and both the DNA fragment and the protein. These results provide an opportunity for these compounds to be studied as potential drug candidates for breast cancer treatment.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Células MCF-7 , Neoplasias de la Mama/metabolismo , Proteína p53 Supresora de Tumor , Simulación del Acoplamiento Molecular , Línea Celular Tumoral , Triazoles/química , Proliferación Celular
5.
J Cell Sci ; 132(20)2019 10 22.
Artículo en Inglés | MEDLINE | ID: mdl-31578236

RESUMEN

Post-translational modifications directly control protein activity and, thus, they represent an important means to regulate the responses of cells to different stimuli. Protein SUMOylation has recently been recognised as one such modification, and it has been associated with various diseases, including different types of cancer. However, the precise way that changes in SUMOylation influence the tumorigenic properties of cells remains to be fully clarified. Here, we show that blocking the SUMO pathway by depleting SUMO1 and UBC9, or by exposure to ginkgolic acid C15:1 or 2-D08 (two different SUMOylation inhibitors), induces cell death, also inhibiting the invasiveness of tumour cells. Indeed, diminishing the formation of SUMO1 complexes induces autophagy-mediated cancer cell death through increasing the expression of Tribbles pseudokinase 3 (TRIB3). Moreover, we found that blocking the SUMO pathway inhibits tumour cell invasion by decreasing RAC1 SUMOylation. These findings shed new light on the mechanisms by which SUMO1 modifications regulate the survival, and the migratory and invasive capacity of tumour cells, potentially establishing the bases to develop novel anti-cancer treatments based on the inhibition of SUMOylation.


Asunto(s)
Muerte Celular Autofágica , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Proteína SUMO-1/metabolismo , Sumoilación , Proteína de Unión al GTP rac1/metabolismo , Humanos , Células MCF-7 , Invasividad Neoplásica , Proteínas de Neoplasias/genética , Neoplasias/genética , Neoplasias/patología , Proteína SUMO-1/genética , Proteína de Unión al GTP rac1/genética
6.
Int J Mol Sci ; 22(10)2021 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-34068980

RESUMEN

Ultraviolet (UV) exposure has been linked to skin damage and carcinogenesis, but recently UVB has been proposed as a therapeutic approach for cancer. Herein, we investigated the cellular and molecular effects of UVB in immortal and tumorigenic HPV positive and negative cells. Cells were irradiated with 220.5 to 1102.5 J/m2 of UVB and cell proliferation was evaluated by crystal violet, while cell cycle arrest and apoptosis analysis were performed through flow cytometry. UVB effect on cells was recorded at 661.5 J/m2 and it was exacerbated at 1102.5 J/m2. All cell lines were affected by proliferation inhibition, cell cycle ablation and apoptosis induction, with different degrees depending on tumorigenesis level or HPV type. Analysis of the well-known UV-responsive p53, E2F1 and microtubules system proteins was performed in SiHa cells in response to UVB through Western-blotting assays. E2F1 and the Microtubule-associated protein 2 (MAP2) expression decrease correlated with cellular processes alteration while p53 and Microtubule-associated Protein 1S (MAP1S) expression switch was observed since 882 J/m2, suggesting they were required under more severe cellular damage. However, expression transition of α-Tubulin3C and ß-Tubulin was abruptly noticed until 1102.5 J/m2 and particularly, γ-Tubulin protein expression remained without alteration. This study provides insights into the effect of UVB in cervical cancer cell lines.


Asunto(s)
Factor de Transcripción E2F1/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de la radiación , Microtúbulos/efectos de la radiación , Proteína p53 Supresora de Tumor/metabolismo , Rayos Ultravioleta , Neoplasias del Cuello Uterino/patología , Apoptosis , Ciclo Celular , Proliferación Celular , Factor de Transcripción E2F1/genética , Femenino , Humanos , Células Tumorales Cultivadas , Proteína p53 Supresora de Tumor/genética , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/radioterapia
7.
Molecules ; 26(17)2021 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-34500773

RESUMEN

Currently, the high added-value compounds contained in plant by-products and wastes offer a wide spectrum of opportunities for their reuse and valorization, contributing to the circular economy. The bell pepper (Capsicum annum L.) is an exotic vegetable with high nutritional value that, after processing, leaves wastes (peel, seeds, and leaves) that represent desirable raw material for obtaining phytochemical compounds. This review summarizes and discusses the relevant information on the phytochemical profile of bell peppers and their related biological properties as an alternative to revalorize losses and wastes from bell peppers for their application in the food and pharmaceutical industries. Bell pepper fruits, seeds, and leaves contain bioactive compounds (phenols, flavonoids, carotenoids, tocopherol, and pectic polysaccharides) that exhibit antioxidant, antibacterial, antifungal, immunosuppressive and immunostimulant properties, and antidiabetic, antitumoral and neuroprotective activities, and have a potential use as functional food additives. In this context, the revalorization of food waste is positioned as a technological and innovative research area with beneficial effects for the population, the economy, and the environment. Further studies are required to guarantee the safety use of these compounds and to understand their mechanisms of action.


Asunto(s)
Capsicum/química , Preparaciones Farmacéuticas/análisis , Fitoquímicos/análisis , Valor Nutritivo , Eliminación de Residuos
8.
Molecules ; 26(20)2021 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-34684686

RESUMEN

A high-order multicomponent reaction involving a six-component reaction to obtain the novel linked 1,5-disubstituted tetrazole-1,2,3-triazole hybrids in low to moderate yield is described. This one-pot reaction is carried out under a cascade process consisting of three sequential reactions: Ugi-azide, bimolecular nucleophilic substitution (SN2), and copper-catalyzed alkyne-azide reaction (CuAAC), with high atom and step-economy due the formation of six new bonds (one C-C, four C-N, and one N-N). Thus, the protocol developed offers operational simplicity, mild reaction conditions, and structural diversity. Finally, to evaluate the antitumoral potential of the synthetized molecules, a proliferation study was performed in the breast cancer (BC) derived cell line MCF-7. The hybrid compounds showed several degrees of cell proliferation inhibition with a remarkable effect in those compounds with cyclohexane and halogens in their structures. These compounds represent potential drug candidates for breast cancer treatment. However, additionally assays are needed to elucidate their complete effect over the cellular hallmarks of cancer.


Asunto(s)
Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Tetrazoles/síntesis química , Triazoles/síntesis química , Antineoplásicos/síntesis química , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Proliferación Celular , Femenino , Humanos , Células MCF-7 , Tetrazoles/farmacología , Triazoles/farmacología
9.
Sociol Perspect ; 64(5): 804-830, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38603057

RESUMEN

Previous research has linked racial/ethnic residential segregation to a number of poor health conditions, including infectious disease. Here, we examine how racial/ethnic residential segregation is related to the novel coronavirus, SARS-CoV-2. We examine infection rates by zip code level segregation in four major cities across the U.S.: New York City, Chicago, Houston, and San Diego. We also include a number of area-level Census variables in order to analyze how other factors may help account for the infection rate. We find that both Black and Latino residential clustering are significantly and positively related to a higher SARS-CoV-2 infection rate across all four cities, and that this effect is strong even when accounting for a number of other social conditions and factors that are salient to the transmission of infectious disease. As a result, we argue that neighborhood-level racial/ethnic patterning may serve as an important structural mechanism for disparities in SARS-CoV-2 infection.

10.
Adv Exp Med Biol ; 1273: 159-173, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33119881

RESUMEN

Mast cells are tissue-resident, innate immune cells that play a key role in the inflammatory response and tissue homeostasis. Mast cells accumulate in the tumor stroma of different human cancer types, and increased mast cell density has been associated to either good or poor prognosis, depending on the tumor type and stage. Mast cells play a multifaceted role in the tumor microenvironment by modulating various events of tumor biology, such as cell proliferation and survival, angiogenesis, invasiveness, and metastasis. Moreover, tumor-associated mast cells have the potential to shape the tumor microenvironment by establishing crosstalk with other tumor-infiltrating cells. This chapter reviews the current understanding of the role of mast cells in the tumor microenvironment. These cells have received much less attention than other tumor-associated immune cells but are now recognized as critical components of the tumor microenvironment and could hold promise as a potential target to improve cancer immunotherapy.


Asunto(s)
Mastocitos/citología , Neoplasias/inmunología , Microambiente Tumoral/inmunología , Humanos , Mastocitos/inmunología
11.
Int J Mol Sci ; 21(15)2020 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-32722549

RESUMEN

Breast cancer (BrC) affects millions of women yearly. Mast cells (MCs) are common components of breast tumors with documented agonistic and antagonistic roles in tumor progression. Understanding the participation of MCs in BrC may lead to new therapies to control tumor growth. In this study, we looked into mechanistic models of MC responses triggered by BrC cells (BrCC), assessing both early degranulation and late transcriptional activities. We used aggressive and non-aggressive BrCC to model the progressive staging of the disease over HMC1 and LAD-2 human MC lines. We found that both MC lines were chemoattracted by all BrCC, but their activation was preferentially induced by aggressive lines, finding differences in their active transcriptional programs, both at basal level and after stimulation. Among those genes with altered expression were down-regulated SPP1, PDCD1, IL17A and TGFB1 and up-regulated KITLG and IFNG. A low expression of SPP1 and a high expression of KITLG and IFNG were associated with increased overall survival of BrC patients from public databases. The set of altered genes is more often associated with tumor stromas enriched with anti-tumoral signals, suggesting that MCs may participate in tumor control.


Asunto(s)
Neoplasias de la Mama/metabolismo , Regulación Neoplásica de la Expresión Génica , Mastocitos/metabolismo , Modelos Biológicos , Proteínas de Neoplasias/biosíntesis , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Bases de Datos Factuales , Supervivencia sin Enfermedad , Femenino , Humanos , Células MCF-7 , Mastocitos/patología , Tasa de Supervivencia
12.
Artículo en Inglés | MEDLINE | ID: mdl-31209011

RESUMEN

Candida albicans is an opportunistic fungal pathogen responsible for mucosal candidiasis and systemic candidemia in humans. Often, these infections are associated with the formation of drug-resistant biofilms on the surfaces of tissues or medical devices. Increased incidence of C. albicans resistance to current antifungals has heightened the need for new strategies to prevent or eliminate biofilm-related fungal infections. In prior studies, we designed 14-helical ß-peptides to mimic the structural properties of natural antimicrobial α-peptides (AMPs) in an effort to develop active and selective antifungal compounds. These amphiphilic, cationic, helical ß-peptides exhibited antifungal activity against planktonic C. albicans cells and inhibited biofilm formation in vitro and in vivo Recent studies have suggested the use of antivirulence agents in combination with antifungals. In this study, we investigated the use of compounds that target C. albicans polymorphism, such as 1-dodecanol, isoamyl alcohol, and farnesol, to attempt to improve ß-peptide efficacy for preventing C. albicans biofilms. Isoamyl alcohol, which prevents hyphal formation, reduced the minimum biofilm prevention concentrations (MBPCs) of ß-peptides by up to 128-fold. Combinations of isoamyl alcohol and antifungal ß-peptides resulted in less than 10% hemolysis at the antifungal MBPCs. Overall, our results suggest potential benefits of combination therapies comprised of morphogenesis modulators and antifungal AMP peptidomimetics for preventing C. albicans biofilm formation.


Asunto(s)
Antifúngicos/farmacología , Biopelículas/efectos de los fármacos , Candida albicans/efectos de los fármacos , Péptidos/farmacología , Antifúngicos/química , Péptidos Catiónicos Antimicrobianos/química , Péptidos Catiónicos Antimicrobianos/farmacología , Candida albicans/crecimiento & desarrollo , Hifa/efectos de los fármacos , Hifa/crecimiento & desarrollo , Pentanoles , Péptidos/química
13.
BMC Cancer ; 19(1): 708, 2019 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-31319816

RESUMEN

BACKGROUND: Mexico City has one of the highest incidences and mortality rates of acute lymphoblastic leukemia (ALL) in the world and a high frequency of early relapses (17%) and early mortality (15%). Otherwise, childhood overweight and obesity are reaching epidemic proportions. They have been associated with poor outcomes in children with ALL. The aim of present study was to identify if overweight and obesity are predictors of early mortality and relapse in Mexican children with ALL. METHODS: A multicenter cohort study was conducted. ALL children younger than 15 years old were included and followed-up during the first 24 months after diagnosis. Overweight and obesity were classified according World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) criteria. Early mortality and early relapses were the main outcomes. RESULTS: A total of 1070 children were analyzed. Overweight/obesity at diagnosis were predictors of early mortality (WHO: HR = 1.4, 95%CI:1.0-2.0; CDC: HR = 1.6, 95%CI:1.1-2.3). However, no associations between overweight (WHO: HR = 1.5, 95%CI:0.9-2.5; CDC: HR = 1.0; 95% CI:0.6-1.6) and obesity (WHO: HR = 1.5, 95%CI:0.7-3.2; CDC: HR = 1.4; 95%CI:0.9-2.3) with early relapse were observed. CONCLUSIONS: Overweight and obese patients embody a subgroup with high risk of dying during leukemia treatment.


Asunto(s)
Obesidad Infantil/epidemiología , Obesidad Infantil/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Adolescente , Índice de Masa Corporal , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Lactante , Masculino , México/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Pronóstico , Recurrencia
14.
Altern Ther Health Med ; 25(4): 54-63, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31202212

RESUMEN

Alcohol catabolism produces oxidative stress, causing cell death and inflammation in liver tissue principally. Hawthorn (Crataegus oxyacantha) and Rosemary (Rosmarinus officinalis) are medicinal plants that have shown a potent antioxidant activity related with anti-inflammatory properties. The objective of this study was the evaluation of Hawthorn and Rosemary methanol extracts as preventive treatment in alcoholic liver disease (ALD). ALD rat model was used to measure serum hepatic enzyme levels (AST, ALT, γ-GT and ACP), total bilirubin, liver glycogen, lipid peroxidation, total antioxidant capacity (TAC) and serum lipid profile (total cholesterol, triglycerides, LDL and HDL) as well as histopathological analysis in hepatic tissues was recorder. Phytotreatments showed preventive effect, decreasing AST, γ-GT, lipid peroxidation and bilirubin indictors while TAC and liver glycogen stores increase. Interestingly, Rosemary diminished the levels of ALT and ACP. Remarkable both treatments show liver tissue damage reduction. Hawthorn proved antihyperlipidemic effect, eviting increase in all lipid indicators, while Rosemary showed antihyperlipidemic effect only in LDL levels without affecting HDL levels. The results indicate that Hawthorn and Rosemary treatments have different mechanisms of action; however they show hepatoprotective effect against ALD in rat model. Hawthorn and Rosemary could be used to prevent or help in the treatment of ALD.


Asunto(s)
Antioxidantes/farmacología , Crataegus/química , Hipolipemiantes/farmacología , Hepatopatías Alcohólicas/tratamiento farmacológico , Hígado/efectos de los fármacos , Rosmarinus/química , Animales , Antioxidantes/uso terapéutico , Hipolipemiantes/uso terapéutico , Hígado/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratas
15.
Int J Mol Sci ; 20(3)2019 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-30696040

RESUMEN

The micro RNA (miR)-34 family is composed of 5p and 3p strands of miR-34a, miR-34b, and miR-34c. The 5p strand's expression and function is studied in cervical cancer. The 3p strand's function and regulation remain to be elucidated. To study the function of the passenger strands of miR-34 family members, we overexpressed 5p and 3p strands using a synthetic miRNA in cervical cell lines. Cell proliferation was evaluated using crystal violet. Migration and invasion were tested using transwell assays, Western blot, and zymography. Possible specific targets and cell signaling were investigated for each strand. We found that miR-34a-5p inhibited proliferation, migration, and cell invasion accompanied by matrix metalloproteinase 9 (MMP9) activity and microtubule-associated protein 2 (MAP2) protein reduction. We also found that miR-34b-5p and miR-34c-5p inhibit proliferation and migration, but not invasion. In contrast, miR-34c-5p inhibits MMP9 activity and MAP2 protein, while miR-34b-5p has no effect on these genes. Furthermore, miR-34a-3p and miR-34b-3p inhibit proliferation and migration, but not invasion, despite the later reducing MMP2 activity, while miR-34c-3p inhibit proliferation, migration, and cell invasion accompanied by MMP9 activity and MAP2 protein inhibition. The difference in cellular processes, MMP2 and MMP9 activity, and MAP2 protein inhibition by miR-34 family members suggests the participation of other regulated genes. This study provides insights into the roles of passenger strands (strand*) of the miR-34 family in cervical cancer.


Asunto(s)
Movimiento Celular/genética , MicroARNs/metabolismo , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Secuencia de Bases , Línea Celular Tumoral , Proliferación Celular/genética , Simulación por Computador , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , Invasividad Neoplásica
16.
Int J Mol Sci ; 20(10)2019 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-31096545

RESUMEN

Acute lymphoblastic leukemia is the most common type of childhood cancer worldwide. Mexico City has one of the highest incidences and mortality rates of this cancer. It has previously been recognized that chromosomal translocations are important in cancer etiology. Specific fusion genes have been considered as important treatment targets in childhood acute lymphoblastic leukemia (ALL). The present research aimed at the identification and characterization of novel fusion genes with potential clinical implications in Mexican children with acute lymphoblastic leukemia. The RNA-sequencing approach was used. Four fusion genes not previously reported were identified: CREBBP-SRGAP2B, DNAH14-IKZF1, ETV6-SNUPN, ETV6-NUFIP1. Although a fusion gene is not sufficient to cause leukemia, it could be involved in the pathogenesis of the disease. Notably, these new translocations were found in genes encoding for hematopoietic transcription factors which are known to play an important role in leukemogenesis and disease prognosis such as IKZF1, CREBBP, and ETV6. In addition, they may have an impact on the prognosis of Mexican pediatric patients with ALL, with the potential to be included in the current risk stratification schemes or used as therapeutic targets.


Asunto(s)
Proteínas de Fusión Oncogénica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Translocación Genética/genética , Adolescente , Adulto , Proteína de Unión a CREB/genética , Niño , Preescolar , Dineínas/genética , Femenino , Proteínas Activadoras de GTPasa/genética , Regulación Neoplásica de la Expresión Génica , Reordenamiento Génico , Humanos , Factor de Transcripción Ikaros/genética , Lactante , Masculino , México , Proteínas Nucleares/genética , Pronóstico , Proteínas Proto-Oncogénicas c-ets/genética , Proteínas de Unión a Caperuzas de ARN/genética , Proteínas de Unión al ARN/genética , Receptores Citoplasmáticos y Nucleares/genética , Proteínas Represoras/genética , Adulto Joven , Proteína ETS de Variante de Translocación 6
17.
Toxicol Mech Methods ; 28(6): 450-460, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29564940

RESUMEN

The metabolism of aromatic hydrocarbons by the organism forms products that cause cell death depending on the type of exposure. Benzene exposure has been linked to oxidative stress, hepatic damage, aplastic anemia, and hematopoietic cancer as lymphoid and myeloid leukemia. However, there are not fast methods to evaluate chronic benzene exposure in human blood. The objective of this work was the evaluation of the correlation between oxidative damage with benzene exposure and the level of cellular plasma membrane stability (CPMS) in erythrocytes to use it as a future indicator to determine the grade of benzene intoxications. CPMS in vitro assays were used to evaluate damage for benzene, toluene, and xylene. Erythrocytes CPMS assays in vitro shows a progressive reduction with benzene, toluene, and xylene suggesting that aromatic hydrocarbons complexity favors CPMS damage. Eight groups of Wistar rats (n = 5) were used to study the level of damage on CPMS by acute and chronic benzene administration. Enzymatic, metabolic, histological, and oxidative damage tests were performed. Acute administration (100 µL/100 g/single dose) showed a decrease of 66.7% in CPMS, while 63.6% for chronic administration (5 µL/100 g/every 2 days/3 months) showing a correlation with liver damage principally (transaminases activity increase, glycogen level decrease, and high oxidative damage). Tissue damage was observed in bone marrow, kidney, spleen, and lungs. Benzene produces damage on CPMS depending on the exposure time and dose. The CPMS technique could be used as an important aromatic hydrocarbons intoxication indicator.


Asunto(s)
Benceno/toxicidad , Membrana Celular/efectos de los fármacos , Eritrocitos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Relación Dosis-Respuesta a Droga , Eritrocitos/metabolismo , Glucógeno/metabolismo , Inyecciones Intraperitoneales , Peroxidación de Lípido/efectos de los fármacos , Masculino , Especificidad de Órganos , Ratas Wistar
18.
Retrovirology ; 14(1): 39, 2017 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-28754126

RESUMEN

BACKGROUND: Insertion of retroviral genome DNA occurs in the chromatin of the host cell. This step is modulated by chromatin structure as nucleosomes compaction was shown to prevent HIV-1 integration and chromatin remodeling has been reported to affect integration efficiency. LEDGF/p75-mediated targeting of the integration complex toward RNA polymerase II (polII) transcribed regions ensures optimal access to dynamic regions that are suitable for integration. Consequently, we have investigated the involvement of polII-associated factors in the regulation of HIV-1 integration. RESULTS: Using a pull down approach coupled with mass spectrometry, we have selected the FACT (FAcilitates Chromatin Transcription) complex as a new potential cofactor of HIV-1 integration. FACT is a histone chaperone complex associated with the polII transcription machinery and recently shown to bind LEDGF/p75. We report here that a tripartite complex can be formed between HIV-1 integrase, LEDGF/p75 and FACT in vitro and in cells. Biochemical analyzes show that FACT-dependent nucleosome disassembly promotes HIV-1 integration into chromatinized templates, and generates highly favored nucleosomal structures in vitro. This effect was found to be amplified by LEDGF/p75. Promotion of this FACT-mediated chromatin remodeling in cells both increases chromatin accessibility and stimulates HIV-1 infectivity and integration. CONCLUSIONS: Altogether, our data indicate that FACT regulates HIV-1 integration by inducing local nucleosomes dissociation that modulates the functional association between the incoming intasome and the targeted nucleosome.


Asunto(s)
Cromatina/metabolismo , Integrasa de VIH/metabolismo , VIH-1/fisiología , Chaperonas de Histonas/metabolismo , Interacciones Huésped-Patógeno , Integración Viral/fisiología , Células Cultivadas , Ensamble y Desensamble de Cromatina/fisiología , Infecciones por VIH/genética , Infecciones por VIH/virología , VIH-1/genética , Humanos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Nucleosomas/metabolismo , Unión Proteica
19.
Int J Mol Sci ; 18(2)2017 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-28216603

RESUMEN

Aberrant miRNA expression is well recognized as a cancer hallmark, nevertheless miRNA function and expression does not always correlate in patients tissues and cell lines studies. In addition to this issue, miRNA strand usage conduces to increased cell signaling pathways modulation diversifying cellular processes regulation. In cervical cancer, 20 miRNA families are involved in carcinogenesis induction and development to this moment. These families have 5p and 3p strands with different nucleotide (nt) chain sizes. In general, mature 5p strands are larger: two miRNAs of 24 nt, 24 miRNAs of 23 nt, 35 miRNAs of 22 nt and three miRNAs of 21 nt. On the other hand, the 3p strands lengths observed are: seven miRNAs of 23 nt, 50 miRNAs of 22 nt, six miRNAs of 21 nt and four miRNAs of 20 nt. Based on the analysis of the 20 miRNA families associated with cervical cancer, 67 3p strands and 65 5p strands are selected suggesting selectivity and specificity mechanisms regulating cell processes like proliferation, apoptosis, migration, invasion, metabolism and Warburg effect. The insight reviewed here could be used in the miRNA based therapy, diagnosis and prognosis approaches.


Asunto(s)
Transformación Celular Neoplásica/genética , MicroARNs/genética , Familia de Multigenes , Neoplasias del Cuello Uterino/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Genes Supresores de Tumor , Humanos , MicroARNs/química , Oncogenes , Interferencia de ARN
20.
J Sci Food Agric ; 97(12): 4117-4123, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28220491

RESUMEN

BACKGROUND: The presence of multidrug-resistant Salmonella in vegetables is a significant public health concern. Nopalito is a cactaceous that is commonly consumed either raw or cooked in Mexico and other countries. The presence of antibiotic-resistant Salmonella strains on raw whole nopalitos (RWN, without prickles), raw nopalitos cut into squares (RNCS) and in cooked nopalitos salads (CNS) samples was determined. In addition, the behavior of multidrug-resistant Salmonella isolates on RWN, RNCS and CNS at 25° ± 2 °C and 3° ± 2 °C was investigated. RESULTS: One hundred samples of RWN, 100 of RNCS and 100 more of CNS were collected from public markets. Salmonella strains were isolated and identified in 30, 30 and 10% of the samples, respectively. Seventy multidrug-resistant Salmonella strains were isolated from all the nopalitos samples. Multidrug-resistant Salmonella isolates survived at least 15 days on RWN at 25° ± 2 °C or 3° ± 2 °C. Multidrug-resistant Salmonella isolates grew in the RNCS and CNS samples at 25° ± 2 °C. However, at 3° ± 2 °C the bacterial growth was inhibited. CONCLUSION: This is the first report about multidrug-resistant Salmonella isolation from raw nopalitos and nopalitos salads. Nopalitos from markets are very likely to be an important factor contributing to the endemicity of multidrug-resistant Salmonella-related gastroenteritis in Mexico. © 2017 Society of Chemical Industry.


Asunto(s)
Farmacorresistencia Bacteriana Múltiple , Contaminación de Alimentos/análisis , Opuntia/microbiología , Salmonella/efectos de los fármacos , Verduras/microbiología , Antibacterianos/farmacología , Microbiología de Alimentos , México , Salmonella/clasificación , Salmonella/genética , Salmonella/aislamiento & purificación
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