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1.
J Enzyme Inhib Med Chem ; 38(1): 2231169, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37401012

ABSTRACT

Trypanosoma cruzi is the causative agent of American trypanosomiasis, which mainly affects populations in Latin America. Benznidazole is used to control the disease, with severe effects in patients receiving this chemotherapy. Previous studies have demonstrated the inhibition of triosephosphate isomerase from T. cruzi, but cellular enzyme inhibition has yet to be established. This study demonstrates that rabeprazole inhibits both cell viability and triosephosphate isomerase activity in T. cruzi epimastigotes. Our results show that rabeprazole has an IC50 of 0.4 µM, which is 14.5 times more effective than benznidazole. Additionally, we observed increased levels of methyl-glyoxal and advanced glycation end products after the inhibition of cellular triosephosphate isomerase by rabeprazole. Finally, we demonstrate that the inactivation mechanisms of rabeprazole on triosephosphate isomerase of T. cruzi can be achieved through the derivatization of three of its four cysteine residues. These results indicate that rabeprazole is a promising candidate against American trypanosomiasis.


Subject(s)
Chagas Disease , Trypanocidal Agents , Trypanosoma cruzi , Humans , Triose-Phosphate Isomerase/chemistry , Triose-Phosphate Isomerase/pharmacology , Rabeprazole/pharmacology , Rabeprazole/therapeutic use , Drug Repositioning , Chagas Disease/drug therapy , Trypanocidal Agents/pharmacology
2.
Plants (Basel) ; 12(12)2023 Jun 14.
Article in English | MEDLINE | ID: mdl-37375939

ABSTRACT

Doubled haploid (DH) technology has become integral to maize breeding programs to expedite inbred line development and increase the efficiency of breeding operations. Unlike many other plant species that use in vitro methods, DH production in maize uses a relatively simple and efficient in vivo haploid induction method. However, it takes two complete crop cycles for DH line generation, one for haploid induction and the other one for chromosome doubling and seed production. Rescuing in vivo induced haploid embryos has the potential to reduce the time for DH line development and improve the efficiency of DH line production. However, the identification of a few haploid embryos (~10%) resulting from an induction cross from the rest of the diploid embryos is a challenge. In this study, we demonstrated that an anthocyanin marker, namely R1-nj, which is integrated into most haploid inducers, can aid in distinguishing haploid and diploid embryos. Further, we tested conditions that enhance R1-nj anthocyanin marker expression in embryos and found that light and sucrose enhance anthocyanin expression, while phosphorous deprivation in the media had no affect. Validating the use of the R1-nj marker for haploid and diploid embryo identification using a gold standard classification based on visual differences among haploids and diploids for characteristics such as seedling vigor, erectness of leaves, tassel fertility, etc., indicated that the R1-nj marker could lead to significantly high false positives, necessitating the use of additional markers for increased accuracy and reliability of haploid embryo identification.

3.
J Environ Manage ; 326(Pt A): 116714, 2023 Jan 15.
Article in English | MEDLINE | ID: mdl-36368202

ABSTRACT

Climate emergency requires urgent actions to reduce carbon emissions. In this paper we calculate the countries' carbon upstreamness and evaluate its linkage to the presence of foreign MNE affiliates, by using a multiregional input-output model with firm heterogeneity. We find a mismatch between carbon upstreamness, emissions reduction targets and income per capita between countries. OECD countries, which are located in the final stages of carbon production, have lower carbon intensity than the world average and have committed strongly to reducing their total emissions. On the contrary, non-OECD countries, which are located mainly in the initial stages of carbon production, maintain higher carbon intensity than the world average and they are less ambitiously committed, as they have lower per capita income. In that context, multinational enterprises (MNEs) could play a key role in supporting the fulfilment of emission reduction targets in host countries, so we propose a simulation to evaluate this role. Specifically, if the MNE affiliates adopt the Intended Nationally Determined Contributions (INDC) set by the controlling country regardless of where they are located, the emissions of MNEs would be reduced by 15.6% (395,864 KtCO2), 4% more than they would be reduced under current emission reduction targets in 2016. However, if MNEs apply the more ambitious INDC, regardless of origin or destination, the emissions would be reduced by 18% (455,910 KtCO2), 7% more than scenario 1 and 1.7% of global emissions in 2016.


Subject(s)
Carbon , Internationality , Carbon Dioxide , Income , Climate
4.
Rev. sanid. mil ; 76(4): e02, oct.-dic. 2022. tab, graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1432136

ABSTRACT

Resumen Las lesiones del psoas ilíaco generan alteraciones metabólicas y modificaciones mecánicas clínicamente relacionadas con dolor, disminución de la flexibilidad, restricción del rango óptimo de movimiento y marcha. El objetivo es presentar la efectividad de los estiramientos con diferentes técnicas sobre la movilidad de cadera, la flexibilidad del músculo iliopsoas y los parámetros biomecánicos de la marcha en niños con déficit de extensión de cadera. Se evaluaron e intervinieron cuatro pacientes: dos del género masculino y dos del femenino, de los 6 a los 11 años, en el Centro de Rehabilitación Infantil de la SEDENA. La valoración fue con análisis de la marcha y del movimiento, posteriormente se les brindó un protocolo de estiramientos por 10 sesiones. Todos los participantes mostraron resultados significativos en los parámetros temporoespaciales de la marcha, demostrando una mayor calidad en la biomecánica de la marcha.


Abstract The lesions of the iliopsoas generate metabolic alterations and mechanical modifications, clinically related to pain, decreased flexibility, restriction of the optimal range of movement and gait. The objective is to present the effectiveness of stretching with different techniques on hip mobility, iliopsoas flexibility and biomechanical gait parameters in children with hip extension deficit. Four patients were evaluated and intervened, two of the male gender and two of the female gender, from 6 to 11 years old, at the Centro de Rehabilitación Infantil of the SEDENA. The assessment was with analysis of gait and movement, then they were given a stretching protocol for 10 sessions. All participants showed significant results in the time-space parameters of gait, demonstrating a higher quality in gait biomechanics.

5.
Appl Microbiol Biotechnol ; 106(4): 1475-1492, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35092453

ABSTRACT

The protease catalytic subunit of the nuclear inclusion protein A from tobacco etch virus (TEVp) is widely used to remove tags and fusion proteins from recombinant proteins. Some intrinsic drawbacks to its recombinant production have been studied for many years, such as low solubility, auto-proteolysis, and instability. Some point mutations have been incorporated in the amino acid protease sequence to improve its production. Here, a comprehensive review of each mutation reported so far has been made to incorporate them into a mutant called TEVp7M with a total of seven changes. This mutant with a His7tag at N-terminus was produced with remarkable purification yields (55 mg/L of culture) from the soluble fraction in a single step affinity purification. The stability of His7-TEVp7M was analyzed and compared with the single mutant TEVp S219V, making evident that His7-TEVp7M shows very constant thermal stability against pH variation, whereas TEVp S219V is highly sensitive to this change. The cleavage reaction was optimized by determining the amount of protease that could cleave a 100-fold excess substrate in the shortest possible time at 30 °C. Under these conditions, His7-TEVp7M was able to cleave His-tag in the buffers commonly used for affinity purification. Finally, a structural analysis of the mutations showed that four of them increased the polarity of the residues involved and, consequently, showed increased solubility of TEVp and fewer hydrophobic regions exposed to the solvent. Taken together, the seven changes studied in this work improved stability, solubility, and activity of TEVp producing enough protease to digest large amounts of tags or fusion proteins. KEY POINTS: • Production of excellent yields of a TEVp (TEVp7M) by incorporation of seven changes. • His-tag removal in an excess substrate in the common buffers used for purification. • Incorporated mutations improve polarity, stability, and activity of TEVp7M.


Subject(s)
Endopeptidases , Chromatography, Affinity , Endopeptidases/genetics , Endopeptidases/metabolism , Proteolysis , Recombinant Fusion Proteins/metabolism
6.
Sci Total Environ ; 805: 150329, 2022 Jan 20.
Article in English | MEDLINE | ID: mdl-34818757

ABSTRACT

Relevant energy questions have arisen because of the COVID-19 pandemic. The pandemic shock leads to emissions' reductions consistent with the rates of decrease required to achieve the Paris Agreement goals. Those unforeseen drastic reductions in emissions are temporary as long as they do not involve structural changes. However, the COVID-19 consequences and the subsequent policy response will affect the economy for decades. Focusing on the EU, this discussion article argues how recovery plans are an opportunity to deepen the way towards a low-carbon economy, improving at the same time employment, health, and equity and the role of modelling tools. Long-term alignment with the low-carbon path and the development of a resilient transition towards renewable sources should guide instruments and policies, conditioning aid to energy-intensive sectors such as transport, tourism, and the automotive industry. However, the potential dangers of short-termism and carbon leakage persist. The current energy-socio-economic-environmental modelling tools are precious to widen the scope and deal with these complex problems. The scientific community has to assess disparate, non-equilibrium, and non-ordinary scenarios, such as sectors and countries lockdowns, drastic changes in consumption patterns, significant investments in renewable energies, and disruptive technologies and incorporate uncertainty analysis. All these instruments will evaluate the cost-effectiveness of decarbonization options and potential consequences on employment, income distribution, and vulnerability.


Subject(s)
COVID-19 , Economic Development , Carbon Dioxide , Communicable Disease Control , Humans , Pandemics , Renewable Energy , SARS-CoV-2 , Socioeconomic Factors
7.
Rev. cuba. ortop. traumatol ; 35(1): e353, 2021. ilus
Article in Spanish | LILACS, CUMED | ID: biblio-1289554

ABSTRACT

Introducción: Las fracturas diafisarias de la tibia tienen una alta incidencia por año, incluidas las del tercio distal. Son las más frecuentes de los huesos largos y se observan sobre todo en adultos jóvenes. Se producen, generalmente, por traumatismos de alta energía como accidentes del tránsito y caídas de alturas. Objetivo: Presentar los resultados del tratamiento realizado a un paciente con fractura extrarticular del tercio distal de la tibia, mediante una técnica de osteosíntesis percutánea mínimamente invasiva. Presentación del caso: Paciente de 45 años, masculino, de piel blanca que sufrió accidente del tránsito, y fue atendido en el servicio de Ortopedia y Traumatología del Hospital General Docente Dr. Antonio Luaces Iraola, con trauma en pierna izquierda. Presentó dolor, inflamación e imposibilidad para caminar. A la exploración física se constató dolor, deformidad, crepitación, movilidad anormal, aumento de volumen e impotencia funcional absoluta. Se realizó radiografía, se corroboró diagnóstico y se decidió tratamiento quirúrgico con técnica mínima invasiva percutánea. Se siguieron los principios de la osteosíntesis biológica y se utilizó placa de segunda generación del sistema AO. Conclusiones: El tiempo quirúrgico fue de 45 minutos, la estadía hospitalaria fue de 48 horas. Se comenzó apoyo parcial a las ocho semanas, y total a las 15 semanas. Se logró la consolidación total de la fractura a las 16 semanas de operado, evaluado de excelente a través de la American Orthopaedic Foot and Ankle Society (AOFAS) score(AU)


Introduction: Diaphyseal fractures of the tibia have high incidence per year, including those of the distal third. They are the most common of the long bones and are seen mostly in young adults. They are generally caused by high-energy trauma such as traffic accidents and falls from heights. Objective: To present the results of the treatment on a patient with extra-articular fracture of the distal third of the tibia, using minimally invasive percutaneous osteosynthesis technique. Case report: A white 45-year-old male patient was injured in a traffic accident, and he was treated in the Orthopedics and Traumatology service at Dr. Antonio Luaces Iraola General Teaching Hospital, because of a trauma to his left leg. He had pain, swelling and inability to walk. Physical examination revealed pain, deformity, crepitus, abnormal mobility, increased volume, and absolute functional impotence. X-rays were performed. The diagnosis was confirmed, and surgical treatment was decided with a minimally invasive percutaneous technique. The principles of biological osteosynthesis were followed and a second generation plate of AO system was used. Conclusions: The surgical time was 45 minutes. The hospital stay was 48 hours. Partial support of the leg was started at eight weeks, and full support at 15 weeks. Full fracture healing was achieved 16 weeks after surgery, the procedure was evaluated as excellent according to the American Orthopedic Foot and Ankle Society (AOFAS) score(AU)


Subject(s)
Humans , Male , Middle Aged , Tibial Fractures/diagnostic imaging
9.
Rev. cuba. ortop. traumatol ; 34(2): e298, jul.-dic. 2020. tab, ilus
Article in Spanish | LILACS, CUMED | ID: biblio-1156592

ABSTRACT

RESUMEN Introducción: Diferentes estudios relacionan el diagnóstico del ultrasonido de alta resolución con el diagnóstico artroscópico del manguito rotador, ambos métodos son favorables y muestran una alta sensibilidad y especificidad al compararlos. Objetivo: Establecer la eficacia diagnóstica entre los hallazgos ecográficos de alta resolución y el diagnóstico artroscópico de rupturas parciales y completas del manguito rotador. Métodos: Se realizó un estudio analítico transversal con el objetivo de evaluar la eficacia diagnóstica del ultrasonido de alta resolución en pacientes del Hospital Provincial General Docente Dr. Antonio Luaces Iraola, de Ciego de Ávila, con diagnóstico clínico de rupturas parciales y completas del manguito rotador, de enero del 2016 a enero del 2019. El universo estuvo constituido por 62 pacientes con diagnóstico clínico de ruptura del manguito rotador que presentaban indicaciones quirúrgicas, a los que se les indicó un estudio imagenológico con ultrasonido de alta resolución y, con posterioridad, se les realizó la intervención quirúrgica por artroscopia, que fue tomada como criterio de verdad. Resultados: Predominó el sexo masculino, con una edad media menor que los del sexo femenino. Los hallazgos diagnósticos por ambos métodos mostraron concordancia en más de dos tercios de los pacientes que presentaron rupturas parciales y completas del espesor del manguito rotador. La ultrasonografía según el método empleado resultó un medio diagnóstico eficaz para las rupturas parciales y completas del espesor del manguito rotador. Conclusiones: El ultrasonido de alta resolución presentó una adecuada correlación en el diagnóstico de lesiones parciales o completas del manguito rotador, confirmada por artroscopia y es considerado un medio diagnóstico eficaz(AU)


ABSTRACT Introduction: Different studies relate the diagnosis of high-resolution ultrasound with the arthroscopic diagnosis of the rotator cuff. Both methods are favorable and show high sensitivity and specificity when they are compared. Objective: To establish diagnostic efficacy between the findings of high-resolution ultrasound and the arthroscopic diagnosis of partial and complete ruptures of the rotator cuff. Methods: A cross-sectional analytical study was carried out, aimed at evaluating the diagnostic efficacy of high-resolution ultrasound in patients of Dr. Antonio Luaces Iraola Provincial General Teaching Hospital, in Ciego de Ávila, with a clinical diagnosis of partial and complete ruptures of the rotator cuff, from January 2016 to January 2019. The universe consisted of 62 patients with a clinical diagnosis of rotator cuff rupture who presented surgical indications, and who were also indicated for an imaging study with high-resolution ultrasound and, subsequently, performed arthroscopic surgery, taken as a criterion of truth. Results: The male sex predominated, with an average age lower than those corresponding to female sex. The diagnostic findings by both methods showed agreement in more than two thirds of the patients who presented partial and complete ruptures of the rotator cuff's thickness. Ultrasonography, according to the method used, was an effective diagnostic tool for partial and complete ruptures of the rotator cuff's thickness. Conclusions: High-resolution ultrasound showed an adequate correlation in the diagnosis of partial or complete ruptures of rotator cuff, as confirmed by arthroscopy. It is considered an effective diagnostic means(AU)


Subject(s)
Humans , Male , Female , Arthroscopy/methods , Ultrasonics/methods , Rotator Cuff Injuries/surgery , Rotator Cuff Injuries/diagnostic imaging , Cross-Sectional Studies
10.
Biomolecules ; 10(7)2020 07 15.
Article in English | MEDLINE | ID: mdl-32679775

ABSTRACT

Therapeutic strategies for the treatment of any severe disease are based on the discovery and validation of druggable targets. The human genome encodes only 600-1500 targets for small-molecule drugs, but posttranslational modifications lead to a considerably larger druggable proteome. The spontaneous conversion of asparagine (Asn) residues to aspartic acid or isoaspartic acid is a frequent modification in proteins as part of the process called deamidation. Triosephosphate isomerase (TIM) is a glycolytic enzyme whose deamidation has been thoroughly studied, but the prospects of exploiting this phenomenon for drug design remain poorly understood. The purpose of this study is to demonstrate the properties of deamidated human TIM (HsTIM) as a selective molecular target. Using in silico prediction, in vitro analyses, and a bacterial model lacking the tim gene, this study analyzed the structural and functional differences between deamidated and nondeamidated HsTIM, which account for the efficacy of this protein as a druggable target. The highly increased permeability and loss of noncovalent interactions of deamidated TIM were found to play a central role in the process of selective enzyme inactivation and methylglyoxal production. This study elucidates the properties of deamidated HsTIM regarding its selective inhibition by thiol-reactive drugs and how these drugs can contribute to the development of cell-specific therapeutic strategies for a variety of diseases, such as COVID-19 and cancer.


Subject(s)
Coronavirus Infections/drug therapy , Enzyme Inhibitors/pharmacology , Neoplasms/drug therapy , Pneumonia, Viral/drug therapy , Small Molecule Libraries/pharmacology , Triose-Phosphate Isomerase/antagonists & inhibitors , Amides/antagonists & inhibitors , Amides/metabolism , COVID-19 , Crystallography, X-Ray , Enzyme Inhibitors/chemistry , Humans , Models, Molecular , Mutation , Pandemics , Proteome/antagonists & inhibitors , Proteome/genetics , Proteome/metabolism , Recombinant Proteins/chemistry , Recombinant Proteins/isolation & purification , Recombinant Proteins/metabolism , Small Molecule Libraries/chemistry , Triose-Phosphate Isomerase/chemistry , Triose-Phosphate Isomerase/metabolism
11.
Sci Rep ; 9(1): 8922, 2019 06 20.
Article in English | MEDLINE | ID: mdl-31222100

ABSTRACT

Research on Giardia lamblia has accumulated large information about its molecular cell biology and infection biology. However, giardiasis is still one of the commonest parasitic diarrheal diseases affecting humans. Additionally, an alarming increase in cases refractory to conventional treatment has been reported in low prevalence settings. Consequently, efforts directed toward supporting the efficient use of alternative drugs, and the study of their molecular targets appears promising. Repurposing of proton pump inhibitors is effective in vitro against the parasite and the toxic activity is associated with the inhibition of the G. lamblia triosephosphate isomerase (GlTIM) via the formation of covalent adducts with cysteine residue at position 222. Herein, we evaluate the effectiveness of omeprazole in vitro and in situ on GlTIM mutants lacking the most superficial cysteines. We studied the influence on the glycolysis of Giardia trophozoites treated with omeprazole and characterized, for the first time, the morphological effect caused by this drug on the parasite. Our results support the effectiveness of omeprazole against GlTIM despite of the possibility to mutate the druggable amino acid targets as an adaptive response. Also, we further characterized the effect of omeprazole on trophozoites and discuss the possible mechanism involved in its antigiardial effect.


Subject(s)
Antiprotozoal Agents/pharmacology , Giardia lamblia/drug effects , Omeprazole/pharmacology , Animals , Enzyme Inhibitors/pharmacology , Enzyme Stability , Giardia lamblia/ultrastructure , Glycation End Products, Advanced/metabolism , Humans , Inhibitory Concentration 50 , Kinetics , Pyruvaldehyde/metabolism , Temperature , Triose-Phosphate Isomerase/antagonists & inhibitors , Triose-Phosphate Isomerase/metabolism
12.
Nat Commun ; 10(1): 1672, 2019 04 11.
Article in English | MEDLINE | ID: mdl-30976001

ABSTRACT

Multinational enterprises (MNE) need to be a part of the solution in the fight against climate change, as claimed by investors and consumers, reducing emissions within their operations and supply chains. This paper measures the carbon footprint of U.S. MNE foreign affiliates (US-MNE) operating beyond the U.S. borders. Using a multiregional input-output model and information about US-MNE activities, the US-MNE carbon footprint ranks US-MNE as the 12th top emitter of the world. In relative terms, one dollar of value added generated by US-MNE affiliates operating abroad requires higher emissions than the domestic average and the ratio increases when only developing host countries are considered. Only 8% of total carbon footprint returns to the U.S. as virtual carbon embodied in the U.S. final consumption. Potential technology transfers between the U.S. parent company and affiliates to reduce US-MNE carbon footprint have been performed to evaluate potential rippled effects of mitigation actions.

13.
Front Plant Sci ; 9: 1527, 2018.
Article in English | MEDLINE | ID: mdl-30405665

ABSTRACT

For efficient production of doubled haploid (DH) lines in maize, maternal haploid inducer lines with high haploid induction rate (HIR) and good adaptation to the target environments is an important requirement. In this study, we present second-generation Tropically Adapted Inducer Lines (2GTAILs), developed using marker assisted selection (MAS) for qhir1, a QTL with a significant positive effect on HIR from the crosses between elite tropical maize inbreds and first generation Tropically Adapted Inducers Lines (TAILs). Evaluation of 2GTAILs for HIR and agronomic performance in the tropical and subtropical environments indicated superior performance of 2GTAILs over the TAILs for both HIR and agronomic performance, including plant vigor, delayed flowering, grain yield, and resistance to ear rots. One of the new inducers 2GTAIL006 showed an average HIR of 13.1% which is 48.9% higher than the average HIR of the TAILs. Several other 2GTAILs also showed higher HIR compared to the TAILs. While employing MAS for qhir1 QTL, we observed significant influence of the non-inducer parent on the positive effect of qhir1 QTL on HIR. The non-inducer parents that resulted in highest mean HIR in the early generation qhir1+ families also gave rise to highest numbers of candidate inducers, some of which showed transgressive segregation for HIR. The mean HIR of early generation qhir1+ families involving different non-inducer parents can potentially indicate recipient non-inducer parents that can result in progenies with high HIR. Our study also indicated that the HIR associated traits (endosperm abortion rate, embryo abortion rate, and proportion of haploid plants among the inducer plants) can be used to differentiate inducers vs. non-inducers but are not suitable for differentiating inducers with varying levels of haploid induction rates. We propose here an efficient methodology for developing haploid inducer lines combining MAS for qhir1 with HIR associated traits.

14.
Front Behav Neurosci ; 12: 202, 2018.
Article in English | MEDLINE | ID: mdl-30233338

ABSTRACT

The effects caused by exposure to lead (Pb) are still considered as a relevant health risk despite public policies aimed to restricting the use of this element. The toxicity limit in the blood (10 µg/dL, established by the Center for Disease Control and Prevention) has been insufficient to prevent adverse effects and even lower values have been related to neurobehavioral dysfunctions in children. Currently, there is not a safe limit of exposure to Pb. A large body of evidence points to environmental pollutant exposure as the cause of predisposition to violent behavior, among others. Considering the evidence by our group and others, we propose that Pb exposure induces alterations in the brain vasculature, specifically in nitric oxide synthases (NOS), affecting in turn the serotonergic system and leading to heightened aggressive behavior in the exposed individuals. This review article describes the consequences of Pb exposure on the nitrergic and serotonergic systems as well as its relationship with aggressive behavior. In addition, it summarizes the available therapy to prevent damage in gestation and among infants.

15.
Mol Cell Biochem ; 437(1-2): 65-80, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28612231

ABSTRACT

Obesity and type II diabetes mellitus have contributed to the increase of breast cancer incidence worldwide. High glucose concentration promotes the proliferation of metastatic cells, favoring the activation of the plasminogen/plasmin system, thus contributing to tumor progression. The efficient formation of plasmin is dependent on the binding of plasminogen to the cell surface. We studied the effect of ε-aminocaproic acid (EACA), an inhibitor of the binding of plasminogen to cell surface, on proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and plasminogen activation system, in metastatic MDA-MB-231 breast cancer cells grown in a high glucose microenvironment and treated with insulin. MDA-MB-231 cells were treated with EACA 12.5 mmol/L under high glucose 30 mmol/L (HG) and high glucose and insulin 80 nmol/L (HG-I) conditions, evaluating: cell population growth, % of viability, migratory, and invasive abilities, as well as the expression of uPA, its receptor (uPAR), and its inhibitor (PAI-1), by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, MMP-2 and MMP-9 mRNAs were evaluated by RT-PCR. Markers of EMT were evaluated by Western blot. Additionally, the presence of active uPA was studied by gel zymography, using casein-plasminogen as substrates. EACA prevented the increase in cell population, migration and invasion induced by HG and insulin, which was associated with the inhibition of EMT and the attenuation of HG- and insulin-dependent expression of uPA, uPAR, PAI-1, MMP-2, MMP-9, α-enolase (ENO A), and HCAM. The interaction of plasminogen to the cell surface and plasmin formation are mediators of the prometastasic action of hyperglycemia and insulin, potentially, EACA can be employed in the prevention and as adjuvant treatment of breast tumorigenesis promoted by hyperglycemia and insulin.


Subject(s)
Aminocaproic Acid/pharmacology , Breast Neoplasms/metabolism , Glucose/pharmacology , Insulin/pharmacology , Neoplasm Proteins , Plasminogen , Breast Neoplasms/pathology , Cell Line, Tumor , Epithelial-Mesenchymal Transition/drug effects , Female , Humans , Neoplasm Invasiveness , Neoplasm Proteins/antagonists & inhibitors , Neoplasm Proteins/metabolism , Plasminogen/antagonists & inhibitors , Plasminogen/metabolism
16.
Theor Appl Genet ; 130(6): 1113-1122, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28315926

ABSTRACT

KEY MESSAGE: Among the qhir11 and qhir12 sub-regions of a major QTL qhir1, only qhir11 has significant effect on maternal haploid induction, segregation distortion and kernel abortion. In vivo haploid induction in maize can be triggered in high frequencies by pollination with special genetic stocks called haploid inducers. Several genetic studies with segregating populations from non-inducer x inducer crosses identified a major QTL, qhir1, on chromosome 1.04 contributing to in vivo haploid induction. A recent Genome Wide Association Study using 51 inducers and 1482 non-inducers also identified two sub-regions within the qhir1 QTL region, named qhir11 and qhir12; qhir12 was proposed to be mandatory for haploid induction because the haplotype of qhir11 was also present in some non-inducers and putative candidate genes coding for DNA and amino acid binding proteins were identified in the qhir12 region. To characterize the effects of each sub-region of qhir1 on haploid induction rate, F2 recombinants segregating for one of the sub-regions and fixed for the other were identified in a cross between CML269 (non-inducer) and a tropicalized haploid inducer TAIL8. To quantify the haploid induction effects of qhir11 and qhir12, selfed progenies of recombinants between these sub-regions were genotyped. F3 plants homozygous for qhir11 and/or qhir12 were identified, and crossed to a ligueless tester to determine their haploid induction rates. The study revealed that only the qhir11 sub-region has a significant effect on haploid induction ability, besides causing significant segregation distortion and kernel abortion, traits that are strongly associated with maternal haploid induction. The results presented in this study can guide fine mapping efforts of qhir1 and in developing new inducers efficiently using marker assisted selection.


Subject(s)
Haploidy , Quantitative Trait Loci , Zea mays/genetics , DNA, Plant/genetics , Gene Frequency , Genetic Association Studies , Genotype , Haplotypes , Phenotype , Recombination, Genetic , Seeds/genetics
17.
Nutr Neurosci ; 20(9): 513-518, 2017 Nov.
Article in English | MEDLINE | ID: mdl-27297776

ABSTRACT

OBJECTIVES: Lead exposure remains a significant environmental problem; lead is neurotoxic, especially in developing humans. In Mexico, lead in human blood is still a concern. Historically, much of the lead exposure is attributed to the use of handcrafted clay pottery for cooking, storing and serving food. However, experimental cause-and-effect demonstration is lacking. The present study explores this issue with a prospective experimental approach. METHODS: We used handcrafted clay containers to prepare and store lemonade, which was supplied as drinking water to pregnant rats throughout the gestational period. RESULTS AND DISCUSSION: We found that clay pots, jars, and mugs leached on average 200 µg/l lead, and exposure to the lemonade resulted in 2.5 µg/dl of lead in the pregnant rats' blood. Neonates also showed increased lead content in the hippocampus and cerebellum. Caspase-3 activity was found to be statistically increased in the hippocampus in prenatally exposed neonates, suggesting increased apoptosis in that brain region. Glazed ceramics are still an important source of lead exposure in Mexico, and our results confirm that pregnancy is a vulnerable period for brain development.


Subject(s)
Aluminum Silicates/chemistry , Cooking and Eating Utensils , Dietary Exposure/adverse effects , Food Contamination , Food Storage/instrumentation , Lead Poisoning, Nervous System/etiology , Lead/toxicity , Animals , Animals, Newborn , Behavior, Animal/drug effects , Cerebellum/drug effects , Cerebellum/metabolism , Citrus/chemistry , Clay , Female , Fruit and Vegetable Juices/adverse effects , Hippocampus/drug effects , Hippocampus/metabolism , Humans , Lead/blood , Lead/metabolism , Lead Poisoning, Nervous System/blood , Male , Maternal Exposure/adverse effects , Mexico , Pregnancy , Random Allocation , Rats, Wistar , Tissue Distribution , Toxicokinetics
18.
Euphytica ; 213: 177, 2017.
Article in English | MEDLINE | ID: mdl-33408421

ABSTRACT

In vivo haploid induction in high frequency followed by efficient identification of haploids are important components of deriving completely homozygous doubled haploid (DH) lines in maize. Several genetic marker systems were proposed and/or used for identification of in vivo maternal haploids in maize, such as R1-nj (Navajo), high oil, red root and transgenic markers. In this study, we propose a new method of haploid/diploid identification based on natural differences in seedling traits of haploids and diploids, which can be used in any induction cross independently of the genetic marker systems. Using confirmed haploids and diploids from five different populations, the study established that haploid and diploid seedlings exhibit significant differences for seedling traits, particularly radicle length (RL), coleoptile length (CL), and number of lateral seminal roots (NLSR). In six populations that exhibited complete inhibition of the commonly used R1-nj (Navajo) marker, we could effectively differentiate haploids from diploids by visual inspection of the seedling traits. In the haploid seed fraction identified based on R1-nj marker in ten populations, false positives were reduced several-fold by early identification of haploids at seedling stage using the seedling traits. We propose that seedling traits may be integrated at the haploid identification stage, especially in populations that are not amenable to use of genetic markers, and for improving the efficiency of DH line production by reducing the false positives.

19.
Mediciego ; 22(4 Suplemento Especial)dic 2016. ilus
Article in Spanish | CUMED | ID: cum-68138

ABSTRACT

Introducción: la rotura del tendón distal del tríceps es una lesión muy infrecuente; representa apenas 0,8 por ciento de todas las lesiones tendinosas. Es frecuente en hombres deportistas, debido probablemente al régimen de entrenamiento. La causa de la lesión es usualmente una caída con la mano en extensión; al estar contraído el tríceps, la fuerza de desaceleración en el brazo ocasiona la rotura.Objetivo: presentar un caso de rotura del tríceps braquial derecho en un atleta de béisbol.Presentación del caso: paciente masculino de 34 años de edad, atleta de béisbol; al capturar un lanzamiento apoyó su mano izquierda y sintió un intenso dolor en la cara posterior del codo izquierdo, lo que le imposibilitó continuar el juego. En el examen físico se constató el signo del hachazo en el tendón distal del tríceps, con aumento de volumen e imposibilidad para extender el codo; la ecografía de partes blandas mostró signos de rotura total del tendón y se orientó tratamiento quirúrgico. En la operación se confirmó la desinserción en el olécranon; se realizó sutura transósea, se inmovilizó el codo a aproximadamente 60 grados de flexión durante seis semanas y posteriormente el paciente comenzó la rehabilitación.Discusión: el paciente no presentó antecedentes patológicos personales ni de infiltraciones con esteroides alrededor del codo; el mecanismo de producción de la lesión fue indirecto, y consecuencia de la práctica deportiva.Conclusiones: la reparación primaria temprana de la lesión es importante porque, independientemente de la técnica quirúrgica empleada, evita recurrir posteriormente a las técnicas de reconstrucción(AU)


Introduction: rupture of the distal triceps tendon is a very uncommon injury; it represents only 0,8 percent of all tendon injuries. It is frequent in athletic men, probably due to their training regimen. The cause of the injury is usually a fall with the hand in extension; when the triceps is contracted, the deceleration force on the arm causes the rupture.Objective: to present a case of right brachial triceps rupture in a baseball athlete.Case presentation: 34-year-old male patient, baseball athlete; when capturing a pitch supported his left hand and felt an intense pain in the back side of the left elbow, which prevented him to continue the game. On physical examination, hatchet strike defect in the distal tendon of the triceps was found, with an increase in volume and impossibility to extend the elbow; ultrasound of soft tissues showed signs of total rupture of the tendon and surgical treatment was oriented. In the operation the deinsertion in the olecranon was confirmed; transosseous suture was performed, the elbow was immobilized at approximately 60 degrees of flexion for six weeks, and then the patient began rehabilitation.Discussion: the patient did not present personal pathological antecedents or infiltrations with steroids around the elbow; the mechanism of production of the injury was indirect, and a consequence of the sport practice.Conclusions: early primary repair of the lesion is important because, regardless of the surgical technique used, it avoids recurring reconstruction techniques(AU)


Subject(s)
Humans , Male , Young Adult , Suture Techniques , Olecranon Process/surgery , Tendon Injuries/surgery , Elbow Joint/surgery , Elbow Joint/injuries , Case Reports
20.
Mediciego ; 22(4 Suplemento Especial)dic 2016. ilus
Article in Spanish | CUMED | ID: cum-68135

ABSTRACT

Introducción: la rotura del tendón del bíceps distal braquial es una lesión poco frecuente; representa sólo 3 por ciento de todas las lesiones del bíceps y afecta principalmente el brazo dominante. Es frecuente en hombres de mediana edad y extremadamente rara en mujeres. En la última década los casos se han incrementado debido al uso de esteroides y el hábito de fumar, entre otros factores de riesgo. Presentación de los casos: se presentan cuatro pacientes con rotura del bíceps distal atendidos en el Servicio de Ortopedia y Traumatología del Hospital Provincial General Docente Dr. Antonio Luaces Iraola. En todos el antecedente de la lesión fue un esfuerzo con el codo flexionado y antebrazo supinado. El tratamiento fue quirúrgico; un paciente fue operado por vía de doble abordaje y los tres restantes por vía anterior; en un caso se realizó fijación transósea, en dos fijación con anclas, y en el cuarto se emplearon ambos métodos. A los cinco meses se permitió la realización de fuerza completa y se orientó seguimiento por 18 meses. Un caso presentó calcificación heterotópica como complicación; la evaluación de los pacientes según la escala de la Clínica Mayo fue de excelente en tres casos y de bien en uno. Conclusiones: la técnica basada en incisión anterior única, con fijación del tendón distal del bíceps al hueso a través de arpones, es eficaz; su tasa de complicaciones es baja. La movilización temprana posibilita que los pacientes retornen más rápido a las actividades de la vida diaria, laboral y deportiva(AU)


Introduction: brachial distal biceps tendon rupture is a rare lesion; it represents only 3 percent of all biceps injuries and mainly affects the dominant arm. It is common in middle-aged men and extremely rare in women. In the last decade cases have increased due to the use of steroids and smoking, among other risk factors. Presentation of cases: four patients with rupture of the distal biceps are presented; they were attended at the Service of Orthopedics and Traumatology of the Provincial General Teaching Hospital Dr. Antonio Luaces Iraola. In all of them the antecedent of the injury was an effort with the elbow flexed and supinated forearm. The treatment was surgical; one patient was operated by double approach and the remaining three by the anterior route; in one case, transosseous fixation was carried out, in two fixation with anchors, and in the fourth, both methods were used. At five months, complete strength was allowed and a follow up for 18 months was indicated. One case presented heterotopic calcification as a complication; the evaluation of patients according to the scale of the Mayo Clinic was excellent in three cases and good in one. Conclusions: the technique based on a single anterior incision, with fixation of the distal biceps tendon to the bone through the harpoons, is effective; its complications rate is low. Early mobilization makes possible for patients to return to activities of daily living, work and sports(AU)


Subject(s)
Humans , Male , Rupture/surgery , Tendon Injuries/surgery , Suture Anchors , Case Reports
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