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A familial reciprocal translocation t(1;15) in three generations identified in a regular trisomy 21 patient

2010 , García-Delgado, C. , Bahena-Martínez, E. , Aparicio-Onofre, A. , Guevara-Yañez, R. , Cervantes-Peredo, A. , Azotla-Vilchis, O. C. , Estrada Mena, Francisco Javier , Luna-Angulo, Alexandra , Villa-Morales, J. , Morrán-Barroso, V. F.

The concurrence of a reciprocal translocation and an aneuploidy represent a rare coincidence and an interchromosome effect between these two events has been suggested. We report the case of a family with a t(1;15) in three generations which was identified through the evaluation ofa patient with classical trisomy 21 or Down syndrome. The cytogenetic analysis with GTG banding showed that the proband had a regular trisomy 21 and a balanced translocation t(1;15). FISH and microsatellite analysis were carried out in the family in order to discard an interchromosomal effect. The implications for genetic assessment are discussed. © Genetic Counseling

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Effects of (−)-epicatechin on frontal cortex DAPC and dysbindin of the mdx mice

2017 , Estrada Mena, Francisco Javier , Rodríguez, Alonso , Mendoza-Lorenzo, Patricia , Neri-Gómez, Teresa , Manjarrez-Gutiérrez, Gabriel , Pérez Ortiz, Andric Christopher , Ordonez-Razo, Rosa , Ceballos, Guillermo , Villarreal, Francisco , Ramírez-Sánchez, Israel

Introduction: Multiple components of the dystrophin-associated protein complex (DAPC) are expressed in numerous tissues including the brain. Members of the DAPC and dysbindin are abnormally expressed in the brain of Duchenne Muscular Dystrophy (DMD) patients, which has been associated with cognitive impairments. However, little is known about the expression pattern of individual members of the DAPC in animal models of DMD and their relationship with dysbindin. Methods: Ten mdx mice were randomly allocated into a control and intervention group [(−)-epicatechin (Epi) 1 mg/kg/day for four weeks] and results compared to a wild-type mice. After sacrifice, brain pre-frontal cortices were collected for Western blotting and immunoprecipitation assays, and sagittal sections processed for immunohistochemistry.

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Assessment of CFH and HTRA1 polymorphisms in age-related macular degeneration using classic and machine-learning approaches

2020 , Martínez Velasco, Antonieta Teodora , Pérez Ortiz, Andric Christopher , Antonio-Aguirre, Bani , Martinez-Villaseñor, Lourdes , Palacio-Pastrana, Claudia , Lira, Esmeralda , Zenteno, Juan Carlos , Ramírez-Sánchez, Israel , Zepeda-Palacio, Claudia , Mendoza Vera, Cristina Azucena , Camacho-Ordóñez, Azyadeh , Ortiz Bibriesca, Daniela , Estrada Mena, Francisco Javier

CFH: and HTRA1 are pivotal genes driving increased risk for age-related macular degeneration (AMD) among several populations. Here, we performed a hospital-based case-control study to evaluate the effects of three single nucleotide polymorphisms (SNPs) among Hispanics from Mexico. Materials and methods: 122 cases and 249 controls were genotyped using Taqman probes. Experienced ophthalmologists diagnosed AMD following the American Association of Ophthalmology guidelines. We studied CFH (rs1329428, rs203687) and HTRA1 (rs11200638) SNPs thoroughly by logistic regression models (assuming different modes of inheritance) and machine learning-based methods (ML). HTRA1: rs11200638 is the most significant polymorphism associated with AMD in our studied population. In a multivariate regression model adjusted for clinically and statistically meaningful covariates, the A/G and A/A genotypes increased the odds of disease by a factor of 2.32 and 7.81, respectively (P < .05) suggesting a multiplicative effect of the polymorphic A allele. Furthermore, this observation remains statistically meaningful in the allelic, dominant, and recessive models, and ML algorithms. When stratifying by phenotype, this polymorphism was significantly associated with increased odds for geographic atrophy (GA) in a recessive mode of inheritance (12.4, p < .05). Conclusions: In sum, this work supports a strong association between HTRA1 genetic variants and AMD in Hispanics from Mexico, especially with GA. Moreover, ML was able to replicate the results of conventional biostatistics methods unbiasedly. © 2020 Taylor & Francis Group, LLC.

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Development of muscle atrophy and loss of function in a Gulf-War illness model: underlying mechanisms

2020 , Ramírez-Sánchez, Israel , Navarrete-Yañez, Viridiana , Garate-Carrillo, Alejandra , Loredo Mendoza, María Lilia , Lira, Esmeralda , Campeau, Anaamika , Estrada Mena, Francisco Javier , González, David , Carrillo-Terrazas, Marvic , Moreno-Ulloa, Aldo , Guillermo Ceballos , Villarreal, Francisco J.

Gulf War illness (GWI) afflicts military personnel who served during the Persian Gulf War and is notable for cognitive deficits, depression, muscle pain, weakness, intolerance to exercise, and fatigue. Suspect causal agents include the chemicals pyridostigmine (PB), permetrim (PM) and N,N-diethyl-m-toluamide (DEET) used as protectants against insects and nerve gases. No pre-clinical studies have explored the effects on skeletal muscle (SkM). Young male rats were provided PB, PM and DEET at equivalent human doses and physical restraint (to induce stress) for 3 weeks followed a 3-week recovery. GWI gastrocnemius weight was ~ 35% lower versus controls, which correlated with decreases in myofiber area, limb strength, and treadmill time/distance. In GWI rats, SkM fiber type relative abundance changed towards slow type I. Muscle wasting pathway proteins were upregulated while those that promote growth decreased as did mitochondrial endpoints and muscle ATP levels. Proteomic analysis of SkM also documented unique alterations in mitochondrial and metabolic pathways. Thus, exposure to GWI chemicals/stress adversely impacts key metabolic pathways leading to muscle atrophy and loss of function. These changes may account for GWI Veterans symptoms.

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Machine learning method to establish the connection between age related macular degeneration and some genetic variations

2016 , Martínez Velasco, Antonieta Teodora , Zenteno, Juan Carlos , Martinez-Villaseñor, Lourdes , Miralles-Pechuán, Luis , Pérez Ortiz, Andric Christopher , Estrada Mena, Francisco Javier

Medicine research based in machine learning methods allows the improvement of diagnosis in complex diseases. Age related Macular Degeneration (AMD) is one of them. AMD is the leading cause of blindness in the world. It causes the 8.7% of blind people. A set of case and controls study could be developed by machine-learning methods to find the relation between Single Nucleotide Polymorphisms (SNPs) SNP_A, SNP_B, SNP_C and AMD. In this paper we present a machine-learning based analysis to determine the relation of three single nucleotide SNPs and the AMD disease. The SNPs SNP_B, SNP_C remained in the top four relevant features with ophthalmologic surgeries and bilateral cataract. We aim also to determine the best set of features for the classification process. © Springer International Publishing AG 2016.

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Comparison of Mutation Profiles in the Duchenne Muscular Dystrophy Gene among Populations: Implications for Potential Molecular Therapies

2015 , López-Hernández, Luz Berenice , Gómez-Díaz, Benjamín , Luna-Angulo, Alexandra , Anaya-Segura, Mónica , Bunyan, David John , Zúñiga-Guzman, Carolina , Escobar-Cedillo, Rosa , Roque-Ramírez, Bladimir , Ruano-Calderón, Luis , Rangel-Villalobos, Héctor , López-Hernández, Julia Angélica , Estrada Mena, Francisco Javier , García, Silvia , Coral-Vázquez, Ramón

Novel therapeutic approaches are emerging to restore dystrophin function in Duchenne Muscular Dystrophy (DMD), a severe neuromuscular disease characterized by progressive muscle wasting and weakness. Some of the molecular therapies, such as exon skipping, stop codon read-through and internal ribosome entry site-mediated translation rely on the type and location of mutations. Hence, their potential applicability worldwide depends on mutation frequencies within populations. In view of this, we compared the mutation profiles of the populations represented in the DMD Leiden Open-source Variation Database with original data from Mexican patients (n = 162) with clinical diagnosis of the disease. Our data confirm that applicability of exon 51 is high in most populations, but also show that differences in theoretical applicability of exon skipping may exist among populations; Mexico has the highest frequency of potential candidates for the skipping of exons 44 and 46, which is different from other populations (p < 0.001). To our knowledge, this is the first comprehensive comparison of theoretical applicability of exon skipping targets among specific populations.

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Blood group O alleles in Native Americans: Implications in the peopling of the Americas

2009 , Estrada-Mena, Benito , Estrada Mena, Francisco Javier , Ulloa-Arvizu, Raúl , Guido, Miriam , Méndez, Rocío , Coral, Ramón , Canto, Thelma , Granados, Julio , Rodrigo Rubí-Castellanos , Rangel-Villalobos, Héctor , García-Carrancá, Alejandro

All major ABO blood alleles are found in most populations worldwide, whereas the majority of Native Americans are nearly exclusively in the O group. O allele molecular characterization could aid in elucidating the possible causes of group O predominance in Native American populations. In this work, we studied exon 6 and 7 sequence diversity in 180 O blood group individuals from four different Mesoamerican populations. Additionally, a comparative analysis of genetic diversity and population structure including South American populations was performed. Results revealed no significant differences among Mesoamerican and South American groups, but showed significant differences within population groups attributable to previously detected differences in genetic drift and founder effects throughout the American continent. Interestingly, in all American populations, the same set of haplotypes O1, O1v, and O1v(G542A) was present, suggesting the following: (1) that they constitute the main genetic pool of the founding population of the Americas and (2) that they derive from the same ancestral source, partially supporting the single founding population hypothesis. In addition, the consistent and restricted presence of the G542A mutation in Native Americans compared to worldwide populations allows it to be employed as an Ancestry informative marker (AIM). Present knowledge of the peopling of the Americas allows the prediction of the way in which the G542A mutation could have emerged in Beringia, probably during the differentiation process of Asian lineages that gave rise to the founding population of the continent. Am J Phys Anthropol, 2010. © 2009 Wiley-Liss, Inc.

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nef/long terminal repeat quasispecies from HIV type 1-infected Mexican patients with different progression patterns and their pathogenesis in hu-PBL-SCID mice

2000 , Gómez-Román, Víctor Raúl , Vásquez, Joel A. , Basualdo, Maria Del Carmen , Estrada Mena, Francisco Javier , Ramos Kuri, Manuel , Soler, Carmen

To examine the genetic features of the long terminal repeat (LTR) derived from six HIV-1-infected individuals enrolled in the Mexico City Cohort, we cloned and sequenced a 505-bp fragment of the proviral LTR from their peripheral blood mononuclear cells (PBMCs). All patients harbored HIV-1 LTR quasispecies corresponding to the B subtype. Three patients with high CD4+ T cell counts (>500/mm3) presented LTR sequences with point mutations in the TAR bulge. The LTR sequence from a patient classified as a long-term nonprogressor (LTNP) presented the most frequent naturally occurring length polymorphism (MFNLP) and two substitutions in the TAR region that were predicted to result in two alternative secondary RNA structures. A novel 18-bp deletion, which eliminates part of the putative binding site for the nuclear factor of activated T cells (NFAT-1), was identified in the overlapping nef/LTR sequence derived from a patient progressing to AIDS. This deletion coincides with the ability of this virus to consistently replicate at low levels in vivo (viral load <500 RNA copies/ml) and in vitro (unsuccessful virus isolation). On one occasion, when virus isolation was successful, the 18-bp deletion was no longer evident and LTR sequences with intact NFAT-1-binding sites were observed. Inoculation of hu-PBL-SCID mice with viruses from several Mexican patients resulted in differential CD4+ T cell depletion patterns 15 days postinfection, which agree with the in vivo CD4+ T cell count data from each patient. © AIDS Research and Human Retroviruses

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Pharmacological Treatments and Therapeutic Targets in Muscle Dystrophies Generated by Alterations in Dystrophin-Associated Proteins

2024 , Alexandra Luna-Angulo , Carlos Landa-Solís , Rosa Elena Escobar-Cedillo , Estrada Mena, Francisco Javier , Laura Sánchez-Chapul , Benjamín Gómez-Díaz , Paul Carrillo-Mora , Hamlet Avilés-Arnaut , Livier Jiménez-Hernández , Dulce Adeí Jiménez-Hernández , Antonio Miranda-Duarte

Muscular dystrophies (MDs) are a heterogeneous group of diseases of genetic origin characterized by progressive skeletal muscle degeneration and weakness. There are several types of MDs, varying in terms of age of onset, severity, and pattern of the affected muscles. However, all of them worsen over time, and many patients will eventually lose their ability to walk. In addition to skeletal muscle effects, patients with MDs may present cardiac and respiratory disorders, generating complications that could lead to death. Interdisciplinary management is required to improve the surveillance and quality of life of patients with an MD. At present, pharmacological therapy is only available for Duchene muscular dystrophy (DMD)—the most common type of MD—and is mainly based on the use of corticosteroids. Other MDs caused by alterations in dystrophin-associated proteins (DAPs) are less frequent but represent an important group within these diseases. Pharmacological alternatives with clinical potential in patients with MDs and other proteins associated with dystrophin have been scarcely explored. This review focuses on drugs and molecules that have shown beneficial effects, mainly in experimental models involving alterations in DAPs. The mechanisms associated with the effects leading to promising results regarding the recovery or maintenance of muscle strength and reduction in fibrosis in the less-common MDs (i.e., with respect to DMD) are explored, and other therapeutic targets that could contribute to maintaining the homeostasis of muscle fibers, involving different pathways, such as calcium regulation, hypertrophy, and maintenance of satellite cell function, are also examined. It is possible that some of the drugs explored here could be used to affordably improve the muscular function of patients until a definitive treatment for MDs is developed.

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Brief inflammatory profile after femtosecond laser-assisted pretreatment in nuclear cataract surgery

2020 , Palacio, Claudia , Pérez Ortiz, Andric Christopher , Antonio-Aguirre, Bani , Mendoza Velásquez, Cristina , Camacho-Ordóñez, Azyadeh , Estrada Mena, Francisco Javier , Orozco-Diaz, Lorena , Lima-Gomez, Virgilio

Purpose : Femtosecond laser-assisted cataract surgery (FLACS) is an FDA-approved treatment with increasing popularity. So far, there are no studies assessing the inflammatory response to FLACS corneal incision, anterior capsulorhexis, and nuclear fragmentation before phacoemulsification in patients exclusively diagnosed with nuclear cataracts. Here, we measured key inflammatory markers in the aqueous humor of patients exposed to femtosecond laser pretreatment. Methods : We performed a cross-sectional study of 67 patients diagnosed with nuclear cataract (LOCS III NO3) undergoing surgery. Of those, 34 were exposed to femtosecond laser pretreatment. At the beginning of the surgery, we collected aqueous humor samples under sterile conditions through a side-port incision. Samples were collected 8 minutes after laser treatment. We measured PgE2 by competitive ELISA, IL-1 β, and IL-6 through cytometric bead arrays. We performed bivariate and stratified analysis in SAS v.9.4. ©Investigative Ophthalmology & Visual Science