10 research outputs found

    Cellular Dynamics Controlled by Phosphatases

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    Protein phosphorylation, a fundamental post-translation modification that acts as a backbone of signaling networks, is essential for multiple aspects of eukaryote physiology. Phosphorylation status of a substrate is dependent on opposing activities of two distinct enzymes, where the relevant kinase catalyzes the modification and is reversed by a phosphatase. Historically, kinases have been at the research forefront; however, phosphatases have gained importance with many studies revealing predominant roles for these enzymes in controlling the cellular responses. Phosphatases are known to attenuate or amplify signaling by operating both as early, as well as delayed regulators of signal transduction. This review is focused on describing the versatile roles of phosphatases in controlling different cellular pathways through their spatio-temporal dynamics during signaling

    First person – Varun Jayeshkumar Shah

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    ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Varun Jayeshkumar Shah is the first author on ‘CRL7SMU1 E3 ligase complex-driven H2B ubiquitination functions in sister chromatid cohesion by regulating SMC1 expression’, published in Journal of Cell Science. Varun is a PhD student in the lab of Dr Subbareddy Maddika at the Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, India, investigating the role of LisH-domain-containing proteins in the assembly of multi-subunit E3 ligase complexes.</jats:p

    METHOD DEVELOPMENT AND VALIDATION OF TIVOZANIB BY USING RP-HPLC IN BULK AND PHARMACEUTICAL DOSAGE FORM

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    Objective: The current investigation was pointed at developing and progressively validating novel, simple, responsive and stable RP-HPLC method for the measurement of active pharmaceutical ingredient of Tivozanib. Methods: A simple, selective, validated and well-defined stability that shows isocratic RP-HPLC methodology for the quantitative determination of Tivozanib. The chromatographic strategy utilized X-bridge phenyl column of dimensions 150x4.6 mm, 3.5 micron, using isocratic elution with a mobile phase of acetonitrile and 0.1 percent formic acid (50:50). A flow rate of 1 ml/min and a detector wavelength of 216 nm utilizing the PDA detector were given in the instrumental settings. Validation of the proposed method was carried out according to an international conference on harmonization (ICH) guidelines. Results: LOD and LOQ for the two active ingredients were established with respect to test concentration. The calibration charts plotted were linear with a regression coefficient of R2&gt;0.999, means the linearity was within the limit. Recovery, specificity, linearity, accuracy, robustness, ruggedness were determined as a part of method validation and the results were found to be within the acceptable range. Conclusion: The proposed method to be fast, simple, feasible and affordable in assay condition. During stability tests, it can be used for routine analysis of the selected drugs

    HACE1 mediated K27 ubiquitin linkage leads to YB-1 protein secretion

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    Ubiquitination is an important post-translational modification that is implicated in controlling almost every biological process by targeting cellular proteins to degradation. While the importance of ubiquitination in controlling the fate and the intracellular functions of various proteins was widely studied, its role in extracellular protein secretion has been unexplored so far. In this study, by using YB-1 (Y-box Binding protein 1) as a model protein, we showed that ubiquitination is required for its extracellular secretion. We also identified HACE1 as a specific E3 ligase that polyubiquitinates YB-1 through non-canonical K27 linked ubiquitin chains. Formation of these ubiquitin linkages on YB-1 is necessary for its interaction with Tumor Susceptibility Gene 101 (TSG101), a component of the Multi-Vesicular Body (MVB) pathway, which facilitates its secretion. Finally, we demonstrated that extracellular secreted YB-1 is a functional protein that acts to inhibit Transforming Growth Factor-Beta mediated epithelial to mesenchymal transition. In summary, we identified a novel functional role for non-canonical ubiquitin linkages in mediating protein secretion

    Removal of Methylene Blue from aqueous solution by activated carbon of <i>Vigna mungo L </i> and <i> Paspalum scrobiculatum</i>: Equilibrium, kinetics and thermodynamic studies.

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    134-144The adsorption capacity of the activated carbons of the agricultural waste materials of Vigna mungo L (Black gram husk - ACBGH) and Paspalum scrobiculatum (Varagu millet Husk - ACVMH) have been explored for the removal of Methylene Blue (MB) from water and was proved to be an efficient adsorbent. The morphology and chemical structure of the adsorbents have been investigated by using Fourier Transform Infrared spectroscopy (FTIR), Scanning Electron Microscopy (SEM) and Brunauer Emmett Teller (BET). Adsorption studies are conducted on a batch process, to study the effects of contact time, initial concentration, temperature and pH. Equilibrium data has been analysed using Langmuir, Freundlich and Dubinin-Radushkevich isotherm models and the monolayer adsorption capacity of the adsorbents are calculated. Kinetic data has been studied using pseudo-first and pseudo-second order kinetic models. The data fits well with the Langmuir model, with a maximum adsorption capacity of 198.40 mg g-1 and 166.30 mg g-1 for ACBGH and ACVMH respectively. The pseudo-second-order kinetics is found to be the best for the adsorption of MB by the adsorbents with good correlation. Thermodynamic studies show that the adsorption is spontaneous, endothermic and entropy controlled. The desorption studies suggest that chemisorptions may be the major mode of adsorption

    Equilibrium, Kinetic and thermodynamic study of adsorption of Safranine O dye from aqueous solution by Bael tree(Aegle marmelos)bark powder

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    Abstract Bael tree bark powder is used as an adsorbent to remove Safranine O (SO) dye from aqueous solutionsThe percentage of Safranine O dye removal, the effects of initial dye concentration, variou s temperatures, contact time, pH influence, and adsorbent dose were examined. An increase in contact time, adsorbent dose, and temperature the betterremoval of SO dye is observed. To examine the equilibrium data, Langmuir and Freundlich adsorption isotherms were applied. The Langmuir adsorption isotherm was used to validate the homogeneous adsorption of SO onto Bael tree bark.The mono layer adsorption capacity of Bael tree bark was found to be 4.88 x 10-4mol/g. Using fictitious first order and second order equations, the kinetic data was examined. The kinetic analyses revealed that chemisorption of the SO dye over the bark of the bael tree powder follows the pseudo-second order (R2 = 0.999). The use of bael tree bark powder for removal of the SO dye can be considered to be the best approach as far as water quality and environmental safety is concerned

    Development of a prototype substitute for subepithelial connective tissue using PCL and Triticum vulgare extract

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    Antecedentes: La reconstrucción de defectos mucogingivales es un desafío significativo en la odontología regenerativa. Las matrices dérmicas acelulares comerciales representan una opción viable, pero su alto costo y disponibilidad limitada motivan el desarrollo de alternativas más accesibles. La técnica de electrospinning permite la generación de fibras poliméricas con potencial para sustituir estas matrices. La policaprolactona (PCL), combinada con Triticum vulgare (TVE) como agente bioactivo, se ha propuesto como un material prometedor debido a sus propiedades mecánicas y biológicas. Objetivo: Este estudio piloto tiene como objetivo evaluar la viabilidad de generar matrices poliméricas mediante electrospinning utilizando PCL y TVE, analizando sus propiedades estructurales, mecánicas, de absorción y porosidad en comparación con un control comercial. Métodos: Se evaluaron seis grupos experimentales que incluyeron combinaciones de PCL al 8% y 10%, con y sin TVE, utilizando diferentes solventes y parámetros de deposición. Las fibras generadas fueron caracterizadas mediante microscopía electrónica de barrido (SEM) para analizar los diámetros y la uniformidad. Las propiedades mecánicas se evaluaron mediante pruebas de tracción para determinar la fuerza máxima y el módulo de Young. Además, se realizaron pruebas de absorción y porosidad para analizar la capacidad de las matrices para retener líquidos y la densidad de los poros. Los resultados estadísticos se analizaron mediante pruebas de Kruskal-Wallis y Wilcoxon Rank-Sum. Resultados: las fibras de PCL al 10% con TVE presentaron diámetros más uniformes y menores (1.62 µm) en comparación con las fibras sin TVE (2.54 µm). En las pruebas mecánicas, estas fibras alcanzaron un módulo de Young intermedio (3.87 MPa), lo que refleja una combinación adecuada de resistencia y flexibilidad. Asimismo, las pruebas de absorción indicaron una alta capacidad de retención de líquidos, mientras que la porosidad alcanzó un máximo del 46.43%, lo que favorece la proliferación celular. En términos de manipulación, las fibras con TVE destacaron por su superioridad en condiciones húmedas, demostrando ser una alternativa práctica y biocompatible frente a los productos comerciales. Conclusiones: Este estudio demuestra que las matrices generadas mediante electrospinning con PCL y TVE poseen características prometedoras para su aplicación en la regeneración mucogingival. La combinación de propiedades estructurales, mecánicas y de absorción posiciona a estas matrices como una alternativa viable para futuras investigaciones, con miras a optimizar los parámetros de fabricación y explorar aplicaciones clínicas más amplias.Grupo de investigación UIBO-Unidad de Investigación Básica OralMagíster en Ciencias OdontológicasMaestríaBackground: The reconstruction of mucogingival defects is a significant challenge in regenerative dentistry. Commercially available acellular dermal matrices represent a viable option, but their high cost and limited availability have driven the development of more accessible alternatives. Electrospinning is a technique that enables the generation of polymeric fibers with the potential to replace these matrices. Polycaprolactone (PCL), combined with Triticum vulgare (TVE) as a bioactive agent, has been proposed as a promising material due to its mechanical and biological properties. Objective: This pilot study aims to evaluate the feasibility of generating polymeric matrices through electrospinning using PCL and TVE, analyzing their structural, mechanical, absorption, and porosity properties in comparison to a commercial control. Methods: Six experimental groups were evaluated, including combinations of PCL at 8% and 10%, with and without TVE, using different solvents and deposition parameters. The generated fibers were characterized by scanning electron microscopy (SEM) to analyze their diameters and uniformity. Mechanical properties were assessed through tensile tests to determine maximum force and Young’s modulus. Additionally, absorption and porosity tests were conducted to analyze the matrices' liquid retention capacity and pore density. Statistical analyses were performed using Kruskal-Wallis and Wilcoxon Rank-Sum tests. Results: PCL fibers at 10% with TVE exhibited more uniform and smaller diameters (1.62 µm) compared to fibers without TVE (2.54 µm). In mechanical tests, these fibers achieved an intermediate Young’s modulus (3.87 MPa), reflecting an adequate combination of strength and flexibility. Furthermore, absorption tests indicated a high liquid retention capacity, while porosity reached a maximum of 46.43%, favoring cell proliferation. In terms of handling, fibers with TVE demonstrated superior performance in wet conditions, proving to be a practical and biocompatible alternative to commercial products. Conclusions: This study demonstrates that matrices generated through electrospinning with PCL and TVE possess promising characteristics for mucogingival regeneration applications. The combination of structural, mechanical, and absorption properties positions these matrices as a viable alternative for future research, aiming to optimize fabrication parameters and explore broader clinical applications

    Search for active principles with neuroprotective potential for the treatment of alzheimer's disease from a species of the gender Zanthoxylum caribaeum (Rutaceae)

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    ilustraciones, fotografías, gráficas, tablasLa Enfermedad de Alzheimer (EA) es la demencia más común, un desorden neurodegenerativo de carácter multifactorial caracterizado por la presencia de placas amiloides, ovillos neurofibrilares, reducción de la actividad colinesterasa, estrés oxidativo, entre otros mecanismos. A pesar de la inversión en investigación durante las últimas décadas, se considera que la investigación debe tomar nuevos enfoques, buscar nuevas dianas biológicas y desarrollar nuevos fármacos, es por ello que en este trabajo se realiza la búsqueda y caracterización de compuestos con actividad multi-diana a partir de productos naturales, teniendo en cuenta que estudios previos de los grupos de investigación demostraron la actividad biológica y el potencial neuroprotector de especies de la familia Rutaceae y particularmente las pertenecientes al género Zanthoxylum de la flora colombiana, las cuales poseen efectos antioxidantes, agonista de LXR e inhibidores de colinesterasas. El objetivo de este trabajo fue realizar una búsqueda de agentes neuroprotectores a partir de la especie Z. caribaeum. Inicialmente se obtuvo un extracto mediante maceración etanólica en frio de la raíz, posteriormente se determinaron el tipo de metabolitos presentes usando técnicas de coloración, se fraccionó el extracto usando cromatografía liquida al vacío (CLV), los compuestos se purificaron usando técnicas cromatográficas, se identificó la estructura química de los compuestos mediante técnicas espectroscópicas y espectrométricas, se evaluó la capacidad antioxidante mediante el método DPPH, y protección del foto-blanqueo del β-caroteno, se evaluó la actividad inhibitoria de acetil y butiril colinestearasas mediante el método Ellman, se realizaron ensayos de viabilidad celular y neuro-protección por MTT, se evaluó la actividad agonista de LXR mediante el ensayo del gen reportero y se determinó la capacidad antiagregante de Aβ de los compuestos mediante un modelo in vitro de cinética de agregación del péptido amiloide. Dentro de los resultados, se logró determinar en el extracto la presencia de metabolitos de tipo alcaloidal, fenólicos, aminas, entre otros. Tanto el extracto como algunas fracciones obtenidas, presentaron actividad agonista de LXR, actividad captadora de radicales libres, protección frente a la peroxidación lipídica y actividad inhibitoria de la butiril colinesterasa; de estas fracciones y mediante el aislamiento químico dirigido, se obtuvo el compuesto 10H-furano [3,2-a] carbazol, el compuesto 5,7 -dimetoxi-4H-cromen-4-ona, y una mezcla de esteroles que contiene estigmasterol y β-sitosterol. El compuesto 10H-furano [3,2-a] carbazol presentó actividad agonista de LXR, se observó efecto neuroprotector y actividad antiagregante de Aβ; el compuesto 5,7 -dimetoxi-4H-cromen-4-ona se reporta por primera vez en esta especie, presenta efecto neuroprotector y actividad antiagregante de Aβ; por su parte, la mezcla de esteroles estigmasterol y β-sitosterol presentó actividad agonista de LXR, efecto neuroprotector y actividad antiagregante de Aβ. Nuestros resultados nos permiten concluir que tanto las fracciones y compuestos aislados de Z. caribaeum presentan un potencial multifuncional para la terapéutica de la EA. (Texto tomado de la fuente).Alzheimer's Disease (AD) is the most common dementia, a multifactorial neurodegenerative disorder characterized by the accumulation of amyloid plaques, neurofibrillary tangles, reduced cholinesterase activity, oxidative stress, among other mechanisms. Despite the investment in research during the last decades, it is considered that research must take new approaches, search for new biological targets and develop new drugs. Here we carry out the search and characterization of compounds with multi-functional activity from Ethanolic extract of Z.caribaeum roots. Previous studies of our research groups demonstrated the biological activity and neuroprotective potential of species of the Rutaceae family and particularly those belonging to the Zanthoxylum genus, which have antioxidant effects, LXR agonist activity and cholinesterase inhibitors. The aim of this work was the search for neuroprotective agents from Zanthoxylum caribaeum. Ethanolic extract of Z.caribaeum roots, was obtained by maceration. The kind of metabolites presents in the extract were determined using coloration assays, the fractionation was carried out using vacuum liquid chromatography (VLC). The compounds were purified by chromatographic techniques, the chemical structures were identified by spectroscopic and spectrometric techniques. The multifunctional potential of ethanolic extract roots, and fractions was determined by antioxidant capacity (DPPH method, and protection from photo-bleaching of β-carotene), inhibitory activity of cholinesterases (acetyl and butyryl cholinesterases), and LXR agonist effect (the gene-reporter assay). In the extract was detected the presence of alkaloidal, phenolic, amines metabolites. The extract and some fractions have LXR agonist activity, free radical scavenging activity, protection against lipid peroxidation, and butyryl cholinesterase inhibitory activity. The compound 10H-furan[3,2-a]carbazole, 5,7-dimethoxy-4H-chromen-4-one, and a mixture of sterols containing stigmasterol and β-sitosterol were isolated and this multifuntional potential was determined by the LXR agonistic activity, Neuroprotective and the Aβ antiaggregating capacity in model in vitro of amyloid peptide aggregation kinetics The compound 10H-furan [3,2-a] carbazole showed LXR agonist activity, neuroprotective effect and antiaggregant activity of Aβ; the compound 5,7-dimethoxy-4H-chromen-4-one is reported for the first time in this species and has a neuroprotective effect and antiaggregant activity of Aβ. Stigmasterol and β-sitosterol presented LXR agonist activity, neuroprotective effect and Aβ antiaggregant activity. Our results allow us to conclude that both the fractions and compounds isolated from Z. caribaeum have multifunctional potential for therapeutics in AD.MaestríaMagíster en NeurocienciasNeurofarmacologí

    Use of PRF VS connective tissue in the VISTA root coverage technique for the treatment of multiple gingival recessions: a systematic review

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    Antecedentes: Recesiones gingivales son comunes en adultos, a menudo requiriendo tratamientos complejos debido a desafíos anatómicos. Las técnicas tradicionales, como el colgajo lateralmente posicionado y el injerto de tejido conectivo (CTG), han evolucionado para mejorar la estética y reducir los riesgos quirúrgicos. Sin embargo, el CTG presenta limitaciones, incluyendo procedimientos más largos y mayor morbilidad. La técnica VISTA, desarrollada por Homa Zadeh, busca minimizar el trauma y mejorar la estética. Recientemente, plasma rico en fibrina (PRF) ha ganado atención como una alternativa regenerativa al CTG, favoreciendo la cicatrización y ofreciendo beneficios potenciales para la cobertura radicular en tratamientos de recesiones gingivales. Objetivo: Comparar mediante una revisión sistemática la cobertura radicular utilizando tejido conectivo frente al uso de PRF en la técnica VISTA para el tratamiento de múltiples recesiones gingivales. Métodos: La metodología emplea una estrategia PICO para definir palabras clave y construir algoritmos de búsqueda en bases de datos. Los criterios de inclusión consideran ensayos clínicos aleatorizados con al menos seis meses de seguimiento en pacientes con múltiples recesiones, excluyendo estudios en animales y artículos sin datos postoperatorios. El análisis de calidad de los artículos se realizó siguiendo el sistema ROB2 de Cochrane, evaluando los cinco dominios propuestos. Los resultados de los artículos originales se compararon considerando los siguientes parámetros: tejido queratinizado y logro de cobertura completa. Resultados: Inicialmente se evaluaron cinco estudios sobre la técnica de Acceso al Túnel Subperióstico con Incisión Vestibular (VISTA) combinada plasma rico en fibrina (PRF) frente al injerto de tejido conectivo (CTG) para recesiones gingivales de Clase I y II. Tras excluir dos estudios, se analizaron tres ensayos clínicos aleatorizados. Los estudios indicaron que la técnica VISTA con CTG es superior en cobertura radicular y aumento de tejido queratinizado, logrando cobertura completa en hasta el 60% de los casos en comparación con el 30.3% con PRF. Aunque ambos tratamientos lograron estabilidad en las recesiones y mejoras estéticas, el CTG mostró mejores resultados globales en parámetros clínicos. El análisis de sesgo reveló que dos estudios presentaron un riesgo moderado, mientras que uno fue de alta calidad, consolidando al CTG como el estándar de oro para la cobertura radicular en el tratamiento de recesiones gingivales. Conclusiones: Los hallazgos indican que el tejido conectivo logra mejores resultados en términos de cobertura radicular completa y parámetros clínicos, reforzando su posición como el estándar de oro. Sin embargo, el PRF emerge como una alternativa menos invasiva con menor morbilidad postoperatoria, promoviendo una cicatrización más rápida y mayor comodidad para el paciente. La técnica VISTA con PRF es particularmente valiosa en casos con tejido donador limitado o cuando la estética y la recuperación postoperatoria son prioridades. Aunque se necesitan más estudios a largo plazo, esta revisión respalda al PRF como un enfoque alternativo viable y personalizable adaptado a las necesidades clínicas y estéticas de los pacientes.Especialista en periodoncia y medicina oralEspecializaciónBackground: Gingival recessions are common in adults, often requiring complex treatments due to anatomical challenges. Traditional techniques like the laterally positioned flap and connective tissue graft (CTG) have evolved to improve aesthetics and reduce surgical risks, but CTG has limitations, including longer procedures and increased morbidity. The VISTA technique, developed by Homa Zadeh, aims to minimize trauma and enhance aesthetics. Recently, platelet-rich fibrin (PRF) has gained attention as a regenerative alternative to CTG, supporting healing and potentially offering benefits for root coverage in gingival recession treatments. Objective: Compare through a systematic review the root coverage using connective tissue vs the use of PRF in the VISTA root coverage technique for the treatment of multiple gingival recessions. Methods: The methodology employs a PICO strategy to define keywords and build research algorithms in databases. Inclusion criteria consider randomized clinical trials with at least six months of follow-up in patients with multiple recessions, excluding animal studies and articles without postoperative data. The quality analysis of the articles was carried out following Chochrane's ROB2 and the 5 proposed domains were evaluated. The results of the original articles were compared considering the following parameters: keratinized tissue, achieving complete coverage. Results: Initially five studies were evaluated on the Vestibular Incision Subperiosteal Tunnel Access (VISTA) technique combined with platelet-rich fibrin (PRF) versus connective tissue graft (CTG) for Class I and II gingival recessions. After excluding two studies, three randomized clinical trials were analyzed. The studies indicated that VISTA with CTG is superior in root coverage and increasing keratinized tissue, achieving complete coverage in up to 60% of cases compared to 30.3% with PRF. Although both treatments achieved recession stability and aesthetic improvements, CTG showed better overall results in clinical parameters. The bias analysis revealed that two studies presented a moderate risk, while one was of high quality, consolidating CTG as the gold standard for root coverage in the treatment of gingival recessions. Conclusions: The findings indicate that connective tissue achieves better outcomes in terms of complete root coverage and clinical parameters, reinforcing its status as the gold standard. However, PRF emerges as a less invasive alternative with lower postoperative morbidity, promoting faster healing and improved patient comfort. The VISTA technique with PRF is particularly valuable in cases with limited donor tissue or when aesthetics and postoperative recovery are priorities. While further long-term studies are needed, this review supports PRF as a viable and customizable alternative approach tailored to the clinical and aesthetic needs of patients
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