CIGB-300, a synthetic peptide-based drug that targets the CK2 phosphoaceptor domain. Translational and clinical research

CK2 represents an oncology target scientifically validated. However, clinical research with inhibitors of the CK2-mediated phosphorylation event is still insufficient to recognize it as a clinically validated target. CIGB-300, an investigational peptide-based drug that targets the phosphoaceptor site, binds to a CK2 substrate array in vitro but mainly to B23/nucleophosmin in vivo. The CIGB-300 proapoptotic effect is preceded by its nucleolar localization, inhibition of the CK2-mediated phosphorylation on B23/nucleophosmin and nucleolar disassembly. Importantly, CIGB-300 shifted a protein array linked to apoptosis, ribosome biogenesis, cell proliferation, glycolisis, and cell motility in proteomic studies which helped to understand its mechanism of action. In the clinical ground, CIGB-300 has proved to be safe and well tolerated in a First-in-Human trial in women with cervical malignancies who also experienced signs of clinical benefit. In a second Phase 1 clinical trial in women with cervical cancer stage IB2/II, the MTD and DLT have been also identified in the clinical setting. Interestingly, in cervical tumors the B23/nucleophosmin protein levels were significantly reduced after CIGB-300 treatment at the nucleus compartment. In addition, expanded use of CIGB-300 in case studies has evidenced antitumor activity when administered as compassional option. Collectively, our data outline important clues on translational and clinical research from this novel peptide-based drug reinforcing its perspectives to treat cancer and paving the way to validate CK2 as a promising target in oncology.Fil: Perea, Silvio E.. Center for Genetic Engineering and Biotechnology; CubaFil: Baladron, Idania. Center for Genetic Engineering and Biotechnology; CubaFil: Garcia, Yanelda. Center for Genetic Engineering and Biotechnology; CubaFil: Perera, Yasser. Center for Genetic Engineering and Biotechnology; CubaFil: Lopez, Adlin. Center for Genetic Engineering and Biotechnology; CubaFil: Soriano, Jorge L.. Center for Genetic Engineering and Biotechnology; Cuba. General Hospital ‘‘Hermanos Ameijeiras’; CubaFil: Batista, Noyde. Center for Genetic Engineering and Biotechnology; Cuba. General Hospital ‘‘Hermanos Ameijeiras’; CubaFil: Palau, Aley. Center for Genetic Engineering and Biotechnology; Cuba. General Hospital ‘‘Hermanos Ameijeiras’; CubaFil: Hernández, Ignacio. Center for Genetic Engineering and Biotechnology; CubaFil: Farina, Hernán Gabriel. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Garcia, Idrian. Center for Genetic Engineering and Biotechnology; CubaFil: Gonzalez, Lidia. Center for Genetic Engineering and Biotechnology; CubaFil: Gil, Jeovanis. Center for Genetic Engineering and Biotechnology; CubaFil: Rodriguez, Arielis. Center for Genetic Engineering and Biotechnology; CubaFil: Solares, Margarita. Center for Genetic Engineering and Biotechnology; CubaFil: Santana, Agueda. Center for Genetic Engineering and Biotechnology; CubaFil: Cruz, Marisol. Center for Genetic Engineering and Biotechnology; CubaFil: Lopez, Matilde. Center for Genetic Engineering and Biotechnology; CubaFil: Valenzuela, Carmen. Center for Genetic Engineering and Biotechnology; CubaFil: Reyes, Osvaldo. Center for Genetic Engineering and Biotechnology; CubaFil: López Saura, Pedro A.. Center for Genetic Engineering and Biotechnology; CubaFil: González, Carlos A.. Center for Genetic Engineering and Biotechnology; CubaFil: Diaz, Alina. Center for Genetic Engineering and Biotechnology; CubaFil: Castellanos, Lila. Center for Genetic Engineering and Biotechnology; CubaFil: Sanchez, Aniel. Center for Genetic Engineering and Biotechnology; CubaFil: Betancourt, Lazaro. Center for Genetic Engineering and Biotechnology; CubaFil: Besada, Vladimir. Center for Genetic Engineering and Biotechnology; CubaFil: González, Luis J.. Center for Genetic Engineering and Biotechnology; CubaFil: Garay, Hilda. Center for Genetic Engineering and Biotechnology; CubaFil: Gómez, Roberto. Center for Genetic Engineering and Biotechnology; CubaFil: Gomez, Daniel Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Perrin, Phillipe. No especifíca;Fil: Renualt, Jean Yves. No especifíca;Fil: Sigman, Hugo. No especifíca;Fil: Herrera, Luis. Center for Genetic Engineering and Biotechnology; CubaFil: Acevedo, Boris. Center for Genetic Engineering and Biotechnology; Cub

El tratamiento de las aguas residuales municipales en las comunidades rurales de México

Recently, efforts have been made to increase municipal wastewater treatment plants in Mexico; however, efforts have focused mainly on urban communities. Municipal wastewater can be treated with different technologies ranging from expensive and highly mechanized equipment to relatively simple and low-cost ecological treatment systems. This paper's aim is to research the current status of municipal wastewater treatment in Mexican rural communities, discussing the main barriers and challenges to overcome in order to increase coverage of treatment plants in these communities. In most states, municipal wastewater treatment plants coverage in small rural communities, with less than 2 500 inhabitants have not been taken care of, especially those 47 233 villages with populations ranging from 100 to 2 499 inhabitants, where it is feasible to install treatment plants. In rural areas, the priority has been given to drinking water supply and sewage, increasing the volumes of wastewater collected. The treatment systems that are most commonly used for the small rural communities with municipal wastewater treatment plants are stabilization ponds and constructed wetlands, followed by sedimentation or septic tanks. Stabilization ponds are quite common in Mexico, whereas constructed wetlands have faced dome barriers preventing their implementationon a larger scale. Some of these obstacles are, deficient knowledge about this technology, lack of basic, easily designed manuals for potential users, etcRecientemente se han hecho esfuerzos, por incrementar la cobertura de plantas de tratamiento de aguas residuales municipales en México; sin embargo, estos esfuerzos se han enfocado principalmente en las comunidades urbanas. Para el tratamiento de aguas residuales municipales, existen diversas tecnologías que van desde las altamente mecanizadas y costosas, hasta las tecnologías relativamente simples y de bajo costo. El objetivo de este trabajo, es investigar el estado actual del tratamiento de las aguas residuales municipales en las comunidades rurales en México, así como discutir cuáles son las barreras y retos que se deben superar, para incrementar la cobertura de plantas de tratamiento. En la mayoría de los estados, se está dejando de atender las pequeñas comunidades rurales de menos de 2 500 habitantes, en especial aquellas 47 233 localidades con 100-2 499 habitantes, en donde es factible instalar plantas de tratamiento. En las zonas rurales se ha dado prioridad a la cobertura de agua potable y los servicios de alcantarillado, lo que ha incrementado el volumen de aguas residuales municipales. Los sistemas de tratamiento que más se emplean en las comunidades rurales, que cuentan con plantas de tratamiento de aguas residuales municipales, son las lagunas de estabilización y los humedales artificiales precedidos de sedimentación o fosa séptica. Mientras que las lagunas de estabilización son bastante comunes en México, los humedales artificiales enfrentan algunas barreras, que han evitado su implementación en forma masiva; por el poco conocimiento de esta tecnología y la falta de diseños accesibles a los usuarios directos

Regeneración de Sedum praealtum A.DC (siempreviva) vía organogénesis

La siempreviva (Sedum praealtum A.DC) pertenece a la familia Crassulaceae, desde hace mucho tiempo ha sido utilizada en la etnobotánica mexicana como un agente anti-inflamatorio y analgésico, en el tratamiento de dolor de dientes, amigdalitis, para enfermedades de los ojos, erupciones cutáneas y de regeneración de tejidos, recientemente se le descubrieron compuestos con actividad antioxidante que presentan efectos hepatoprotector y anticancerígeno. Se estableció un protocolo eficiente de regeneración mediante organogénesis para Sedum praealtum a partir de hojas jóvenes de plantas provenientes de vivero. Fragmentos de hoja que contenían la parte media se cultivaron en medio Murashige y Skoog adicionado con bencilaminopurina (6-BAP) y 2,4-Diclorofenoxiacético (2,4-D) en varias combinaciones. A los 90 días de haber iniciado el cultivo, el tratamiento suplementado con 0.5 mg/L de 6-BAP, 0.0 mg/L de 2,4-D mostró efectos significativos sobre el desarrollo de órganos por la vía indirecta, dando en promedio 13.0±0.3 brotes por explante. Los brotes se individualizaron y se transfirieron a medio MS suplementado con 2.0 mg/L de ácido indolacético (AIA) para su enraizamiento.Siempreviva (Sedum praealtum A. DC) belongs to the Crassulaceae family, it has long been used in Mexican ethnobotanical as an anti-inflammatory and analgesic agent in the treatment of toothache, tonsillitis, for eyes diseases, sking and tisuue regeneration eruption, was recently discovered antioxidant compounds havings hepatoprotective and anticancer effects. An efficient protocol for organogenesis regeneration was established for Sedum praealtum from young leaves of nursery plants. Leaf segment that contained the middle portion of the leaf were cultured on Murashige and Skoog medium supplemented with different combintions of 6-Benzylaminopurine (6-BAP) and 2,4-Dichlorophenoxyacetic acid (2,4-D). 90 days after culture, the highest shoot induction was observed on MS medium supplemented with 0.5 mg/L 6-BAP and 0.0 mg/L 2,4-D with 13.0±0.3 shoot per explant. Shoot were individualized and transferred to MS médium supplemented with 2.0 mg/L Indoleacetic acid (IAA) for rooting

Relaciones genéticas basadas en marcadores ISTR entre formas silvestres, cultivadas e intermedias de frijol de guía colectado en Jalisco, México

Background and Aims: In the climbing beans (Phaseolus vulgaris) three main forms are distinguished: cultivated, semi-wild and wild. The concept of form is used as a hierarchical category within a species according to morphological and genetic divergence, ecogeographic distribution, possibilities of hybridization and fertility of hybrids and derivatives. The objective was to investigate the genetic relationships between wild, semi-wild and cultivated bean populations from a region in western Mexico. Methods: An analysis of 30 common bean accessions with the molecular marker ISTR (Inverse Sequence Tagged Repeat) was realized, based on sequences of retrotransposons copia-like. The similarity among individual plants was calculated with Jaccard’s coefficient. Genetic structure was determined using a probabilistic Bayesian model. Key results: A high level of genetic differentiation (FST) was determined between cultivated and wild beans. The number of groups associated with hybridization was inferred, based on the similarity coefficient method. Analysis of genetic structure detected nine groups within the material studied. The ISTR marker is presented as an effective marker to distinguish between cultivated and wild material and establish the degree of similarity between accessions. Conclusions: Cultivated beans were associated with semi-wild accessions and clearly separated from wild ones. This information generates valuable data for the characterization of the genetic variability of this resource, as well as for assessing germplasm conditions for conservation and breeding programs.Antecedentes y Objetivos: En el frijol de guía (Phaseolus vulgaris) se distinguen tres formas principales: cultivada, intermedia y silvestre. El concepto de forma se utiliza como categoría jerárquica dentro de una especie de acuerdo a la divergencia morfológica y genética, distribución ecogeográfica, posibilidades de hibridación y fertilidad de los híbridos y sus derivados. El objetivo fue detectar las relaciones genéticas entre poblaciones silvestres, intermedias y cultivadas provenientes de una región en el occidente de México. Métodos: Se realizó un análisis en 30 poblaciones de frijol común de guía con datos moleculares obtenidos con el marcador ISTR (Inverse Sequence Tagged Repeat), basado en secuencias de retrotransposones copia-like. Se calculó la similitud por coeficiente de Jaccard entre cada planta analizada. Se determinó la estructura genética usando el modelo Bayesiano probabilístico. Resultados clave: Se encontró un alto grado de diferenciación genética (FST) entre las formas cultivadas y las silvestres. Se infirió el número de grupos asociados a la hibridación entre los materiales, basados en el coeficiente de similitud. El análisis de estructura genética detectó nueve grupos dentro del material estudiado. El marcador ISTR se presenta como un marcador efectivo para diferenciar material cultivado del silvestre y establecer grados de similitud entre las accesiones. Conclusiones: Se detectaron asociaciones entre las variedades cultivadas y accesiones intermedias, así como una clara separación de las cultivadas de las silvestres. Esta información genera datos valiosos para la caracterización de la variabilidad genética de este recurso, así como la obtención de datos importantes para el diseño de planes de conservación y mejoramiento

Regeneración de Sedum praealtum A.DC (siempreviva) vía organogénesis

Introduction: Dalbergia congestiflora Pittier (campincerán) is used to make musical instruments in Michoacán (Mexico), so this specie is considered overexploited and at risk of extinction. Propagation studies of campincerán are scarce, but the factors that could affect the propagation by stem cuttings of this species are auxin exogenous concentration and position of the stem cuttings (apical, media and basal). The hypothesis tested is that a higher sprouting and rooting at concentrations between 1 and 10 ppm of indolbutyric acid (IBA) and the basal stem cuttings are observed. Method: The stem cuttings of D. congestiflora were collected in Tacámbaro, Michoacán. The apical, middle and basal cuttings were placed in a rooting solution of 1, 5 and 10 ppm of IBA. The variables studied were the sprouting percentage, the mean number of sprouts and the mean length of the sprouts after 15, 45 and 75 days, while the percentage of rooting was evaluated after 150 days. Results: The sprouting percentage, mean number of sprouts and mean length of sprouts were higher in basal cuttings in relation to the apical and meddle cuttings. The rooting was observed only at basal cuttings with 10 ppm of IBA. Conclusion: The sprouting of cuttings was observed at low cocentrations of IBA and this is independent of position stem cuttings, but the rooting occurred only at 10 ppm of IBA

Organogénesis indirecta y enraizamiento "in vitro" de "Paulownia elongata"

En este estudio se evaluó el efecto de la combinación de tres factores sobre la organogénesis indirecta de "Paulownia elongata". Los explantes se cultivaron durante 4 semanas en una serie de tratamientos que resultaron de combinar los siguientes factores: Factor I, medios de cultivo: MS y WPM. Factor II, reguladores de crecimiento: concentraciones de 5 y 10 mg·l[-1] de BA, 0.5 mg·l[-1] de ANA, 1 y 8 mg·l[-1] de TDZ, 0.1 mg·l[-1] de KIN. Factor III, tipo de explante: segmento de hoja con pecíolo (P) y segmento central de la hoja (C). Además, se evaluó el efecto de diferentes agentes enraizadores sobre los brotes obtenidos, se utilizó un agente químico (1.5 mg·l[-1] de AIB), uno físico (luz roja a 660 nm) y otro biológico ("Agrobacterium rhizogenes"). La producción de brotes fue más alta en el tratamiento suplementado con 10 mg·l[-1] de BA y 0.5 mg·l[-1] de ANA en el medio MS, se empleó el tipo de explante (P), donde la producción de brotes después de 4 semanas en cultivo se presentó en el 80%. Se analizó el efecto de diferentes enraizadores mediante la evaluación de las variables de respuesta número de raíces por explante, longitud de la raíz más larga, altura de la planta, diámetro del tallo y número de hojas por explante. El agente químico (1.5 mg·l[-1] de AIB) resultó el más efectivo para las variables número de raíces por explante, altura de la planta y número de hojas por explante, mientras que para la variable longitud de la raíz más larga su efecto fue similar al del agente físico y al control. La respuesta a la variable del diámetro del tallo fue similar para el agente químico y el control

Evaluation of Somaclonal and Ethyl Methane Sulfonate-Induced Genetic Variation of Mexican Oregano (<i>Lippia graveolens</i> H.B.K.)

Lippia graveolens, commonly known as Mexican oregano, is an aromatic plant of great industrial, nutritional, and medicinal value, principally for its essential oils. Regeneration via axillary buds was established in MS medium supplemented with 6-benzyladenine (BA) (0.5 mgL&#8722;1) as a growth regulator. Three genotypes and three stages of cultivation were considered in the study. On average, 3.5, 4.2, and 6.4 shoots induced per explant were obtained for genotypes B, C, and D, respectively. Several doses (0.1, 0.3, and 0.5%) of ethyl methane sulfonate (EMS) and different exposure times (1, 2, and 3 h) were applied to investigate the effect of the chemical mutagen on the formation of axillary buds. Genetic variation among the collected plants, the micro-propagated plants during three sub-cultivations, and the plants regenerated in the presence of the mutagen was evaluated by means of randomly amplified microsatellite polymorphism (RAMP) markers. A high genetic stability was observed in the micro-propagation of Mexican oregano for the three genotypes and three sub-cultivations, presenting 100% of monomorphic bands. The genetic variation observed in the different collections of wild populations (A, R, and V) and after treatment with EMS regarded 34 and 35% of polymorphic loci, respectively