RESUMEN
The Starmerella bombicola lactone esterase (SBLE) is a novel enzyme that, in vivo, catalyzes the intramolecular esterification (lactonization) of acidic sophorolipids in an aqueous environment. In fact, this is an unusual reaction given the unfavorable conditions for dehydration. This characteristic strongly contributes to the potential of SBLE to become a 'green' tool in industrial applications. Indeed, lactonization occurs normally in organic solvents, an application for which microbial lipases are increasingly used as biocatalysts. Previously, we described the production of recombinant SBLE (rSBLE) in Pichia pastoris (syn. Komagataella phaffii). However, expression was not optimal to delve deeper into the enzyme's potential for industrial application. In the current study, we explored codon-optimization of the SBLE gene and we optimized the rSBLE expression protocol. Temperature reduction had the biggest impact followed by codon-optimization and co-expression of the HAC1 transcription factor. Combining these approaches, we achieved a 32-fold improvement of the yield during rSBLE production (from 0.75 mg/l to 24 mg/L culture) accompanied with a strong reduction of contaminants after affinity purification.
Asunto(s)
Esterasas/metabolismo , Proteínas Fúngicas/metabolismo , Proteínas Recombinantes/metabolismo , Saccharomycetales/enzimología , Codón/genética , Esterasas/química , Esterasas/genética , Esterasas/aislamiento & purificación , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Proteínas Fúngicas/aislamiento & purificación , Tecnología Química Verde , Lactonas/metabolismo , Pichia/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Saccharomycetales/genética , TemperaturaRESUMEN
Cancer-related fatigue (CRF) is the most commonly reported symptom in patients with cancer with a prevalence up to 100%. It has a significant negative impact on quality of life. An effective management of CRF could significantly reduce the disease burden associated with cancer and its treatment. Unfortunately, the underlying pathophysiology is very complex and not uniform. This article reviews the possible therapy of contributing factors, nonpharmacological treatment, such as exercise and psychosocial interventions, and pharmacologic approaches in managing CRF. Numerous drugs, such as psychostimulants (methylphenidate, dexamphetamines, modafinil and pemoline), antidepressants, corticosteroids, L-carnitine, donepezil and guarana have been studied. Methylphenidate, modafinil and guarana show the most promising results so far. However, additional randomized, placebo-controlled trials are needed to determine the benefit of these and other drugs in the treatment of CRF.
Asunto(s)
Fatiga/etiología , Fatiga/terapia , Neoplasias/complicaciones , Fatiga/diagnóstico , HumanosAsunto(s)
Trasplante de Células Madre/efectos adversos , Tirotoxicosis/etiología , Tirotoxicosis/terapia , Enfermedad Aguda , Adulto , Femenino , Enfermedades Hematológicas/complicaciones , Enfermedades Hematológicas/terapia , Humanos , Masculino , Factores de Riesgo , Resultado del Tratamiento , Irradiación Corporal Total/efectos adversosRESUMEN
We report a case of lymphocytic colitis in a 74-year-old woman presenting with watery diarrhea since 1 year and in whom previous extensive investigations were normal. The diagnosis could be made on the basis of typical pathological pattern in colonic biopsies. The outcome was favourable with salazopyrine therapy. The clinical, histological and pathophysiological aspects of lymphocytic colitis are discussed.