ABSTRACT
Current standard adjuvant therapy of glioblastoma multiforme (GBM) using temozolomide (TMZ) frequently fails due to therapy resistance. Thus, novel therapeutic approaches are highly demanded. We tested the therapeutic efficacy of the second-generation XPO1 inhibitor Eltanexor using assays for cell viability and apoptosis in GBM cell lines and GBM stem-like cells. For most GBM-derived cells, IC50 concentrations for Eltanexor were below 100 nM. In correlation with reduced cell viability, apoptosis rates were significantly increased. GBM stem-like cells presented a combinatorial effect of Eltanexor with TMZ on cell viability. Furthermore, pretreatment of GBM cell lines with Eltanexor significantly enhanced radiosensitivity in vitro. To explore the mechanism of apoptosis induction by Eltanexor, TP53-dependent genes were analyzed at the mRNA and protein level. Eltanexor caused induction of TP53-related genes, TP53i3, PUMA, CDKN1A, and PML on both mRNA and protein level. Immunofluorescence of GBM cell lines treated with Eltanexor revealed a strong accumulation of CDKN1A, and, to a lesser extent, of p53 and Tp53i3 in cell nuclei as a plausible mechanism for Eltanexor-induced apoptosis. From these data, we conclude that monotherapy with Eltanexor effectively induces apoptosis in GBM cells and can be combined with current adjuvant therapies to provide a more effective therapy of GBM.
ABSTRACT
Depression is a common and debilitating mood disorder that increases in prevalence during pregnancy. Worldwide, 7 to 12% of pregnant women experience depression, in which the associated risk factors include socio-demographic, psychological, and socioeconomic variables. Maternal depression could have psychological, anatomical, and physiological consequences in the newborn. Depression has been related to a downregulation in serotonin levels in the brain. Accordingly, the most commonly prescribed pharmacotherapy is based on selective serotonin reuptake inhibitors (SSRIs), which increase local serotonin concentration. Even though the use of SSRIs has few adverse effects compared with other antidepressants, altering serotonin levels has been associated with the advent of anatomical and physiological changes in utero, leading to defects in craniofacial development, including craniosynostosis, cleft palate, and dental defects. Migration and proliferation of neural crest cells, which contribute to the formation of bone, cartilage, palate, teeth, and salivary glands in the craniofacial region, are regulated by serotonin. Specifically, craniofacial progenitor cells are affected by serotonin levels, producing a misbalance between their proliferation and differentiation. Thus, it is possible to hypothesize that craniofacial development will be affected by the changes in serotonin levels, happening during maternal depression or after the use of SSRIs, which cross the placental barrier, increasing the risk of craniofacial defects. In this review, we provide a synthesis of the current research on depression and the use of SSRI during pregnancy, and how this could be related to craniofacial defects using an interdisciplinary perspective integrating psychological, clinical, and developmental biology perspectives. We discuss the mechanisms by which serotonin could influence craniofacial development and stem/progenitor cells, proposing some transcription factors as mediators of serotonin signaling, and craniofacial stem/progenitor cell biology. We finally highlight the importance of non-pharmacological therapies for depression on fertile and pregnant women, and provide an individual analysis of the risk-benefit balance for the use of antidepressants during pregnancy.
ABSTRACT
The age and growth rate of the giant electric ray, Narcine entemedor, was estimated using growth bands deposited in the vertebral centra of 245 specimens. Differences in size and age distribution were found between the sexes, a pattern that suggests the annual deposition of band pairs, possibly occurring in April. Multimodel inference and back-calculation were performed to three age data sets of females considering their reproductive cycle and time of capture, among which the von Bertalanffy growth function was found to be the most appropriate (L∞ = 81.87 cm TL, k = 0.17 year-1). Our research supports the idea that age can be determined via biological features such as birth date and growth band periodicity. We concluded that N. entemedor is of a moderate body size, moderate longevity and is a fast-growing elasmobranch species.
ABSTRACT
De 1988 a 1993 se muestrearon 1030 ejemplares de marlin rayado (Tetrapturus audax )capturados por la flota deportiva de Cabo San Lucas.Se recolectaron 389 espinas dorsales para la estimación de la edad.La relación Longitud mandibular-Radio total de la espina es similar para hembras y machos.Se encontró que la cuarta espina dorsal refleja adecuadamente el crecimiento.La periodicidad de formación de las marcas de crecimiento es anual y parece que se relaciona con la temperatura superficial promedio del mar.Se contaron las bandas opaco-hialinas en cada corte de las espinas,y se encontraron diez grupos de edad (del dos al once),siendo el grupo siete el más abundante, seguido por los grupos seis y ocho.Las tallas observadas para el marlin rayado fueron de 160-280 cm de longitud mandibular,el 90%de los organismos estuvieron entre 190 y 225 cm.Los ejemplares pequeños se incorporan a la pesquería de junio hasta diciembre
The striped marlin (Tetrapturus audax)is found in temperate and tropical waters of the Pacific and Indian Ocean.It is particularly abundant in the southern tip of the Baja California peninsula.Specimens brought to Cabo San Lucas port (22 °53 N y 109 °54 W)by the sport fishery fleet that operates withing a radius of 54 km from 1988 to 1993 were sexes,measured and weighed.A total 1030 individuals were sampled.Dorsal fin spines (389)were collected for age estimation.The spines were sectioned and hyaline-opaque bands counted.The relation of length to spine radius was similar for males and females.The fourth dorsal spine reflected the growth of the fish.The rhythm of growth mark formation is yearly and related to the sea surface temperature.Ten age groups were found and the seventh group was the most abundant,followed by groups "6 "and "8 ".The age structure of the striped marlin was stable in the study period.The observed sizes were 160-280 cm jaw length with 90%of the organisms measuring between 190 and 225 cm.The small individuals recruit to the fishery from June to December
Subject(s)
Animals , Fisheries , Perciformes/anatomy & histology , Seawater , Body Weight , Longevity , Mexico , Pacific Ocean , Perciformes/growth & development , Perciformes/physiology , Temperature , Time FactorsABSTRACT
The striped marlin (Tetrapturus audax) is found in temperate and tropical waters of the Pacific and Indian Ocean. It is particularly abundant in the southern tip of the Baja California peninsula. Specimens brought to Cabo San Lucas port (22 degrees 53' N y 109 degrees 54' W) by the sport fishery fleet that operates withing a radius of 54 km from 1988 to 1993 were sexes, measured and weighed. A total 1030 individuals were sampled. Dorsal fin spines (389) were collected for age estimation. The spines were sectioned and hyaline-opaque bands counted. The relation of length to spine radius was similar for males and females. The fourth dorsal spine reflected the growth of the fish. The rhythm of growth mark formation is yearly and related to the sea surface temperature. Ten age groups were found and the seventh group was the most abundant, followed by groups "6" and "8". The age structure of the striped marlin was stable in the study period. The observed sizes were 160-280 cm jaw length with 90% of the organisms measuring between 190 and 225 cm. The small individuals recruit to the fishery from June to December.
