Protein Plasma Levels of the IGF Signalling System Are Altered in Major Depressive Disorder.

The Insulin-like growth factor 2 (IGF-2) has been recently proven to alleviate depressive-like behaviors in both rats and mice models. However, its potential role as a peripheral biomarker has not been evaluated in depression. To do this, we measured plasma IGF-2 and other members of the IGF family such as Binding Proteins (IGFBP-1, IGFBP-3, IGFBP-5 and IGFBP-7) in a depressed group of patients (n = 51) and in a healthy control group (n = 48). In some of these patients (n = 15), we measured these proteins after a period (19 ± 6 days) of treatment with antidepressants. The Hamilton Depressive Rating Scale (HDRS) and the Self-Assessment Anhedonia Scale (SAAS) were used to measure depression severity and anhedonia, respectively. The general cognition state was assessed by the Mini-Mental State Examination (MMSE) test and memory with the Free and Cued Selective Reminding Test (FCSRT). The levels of both IGF-2 and IGFBP-7 were found to be significantly increased in the depressed group; however, only IGF-2 remained significantly elevated after correction by age and sex. On the other hand, the levels of IGF-2, IGFBP-3 and IGFBP-5 were significantly decreased after treatment, whereas only IGFBP-7 was significantly increased. Therefore, peripheral changes in the IGF family and their response to antidepressants might represent alterations at the brain level in depression.

Immunogenicity and safety of a RBD vaccine against SARS-CoV-2 in a murine model.

INTRODUCTION: Although more than half of the world's population is already vaccinated, the appearance of new variants of concern puts public health at risk due to the generation of new immunogens against the virus as a crucial and relevant strategy in the control of these new variants. METHODS: A preclinical study used a potential vaccine candidate (RBD, SARS-CoV-2). Four groups of BALB/c mice were used, a control group, an adjuvant group, a group inoculated with one dose of RBD subunit protein, and the fourth group inoculated with two doses of RBD subunit protein. RESULTS: No inflammatory or cellular changes were shown in the mice's anatomopathological evaluation. Higher kinetics and 75% seroconversion were obtained in the mice inoculated with two doses of RBD (P < 0.0001). CONCLUSIONS: The application of two doses of the RBD vaccine candidate in BALB/c mice proved safe and immunogenic against SARS-CoV-2.

Therapeutic Approaches in Lysosomal Storage Diseases.

Lysosomal Storage Diseases are multisystemic disorders determined by genetic variants, which affect the proteins involved in lysosomal function and cellular metabolism. Different therapeutic approaches, which are based on the physiologic mechanisms that regulate lysosomal function, have been proposed for these diseases. Currently, enzyme replacement therapy, gene therapy, or small molecules have been approved or are under clinical development to treat lysosomal storage disorders. The present article reviews the main therapeutic strategies that have been proposed so far, highlighting possible limitations and future perspectives.

The New Pharmacological Chaperones PBXs Increase α-Galactosidase A Activity in Fabry Disease Cellular Models.

Fabry disease is an X-linked multisystemic disorder caused by the impairment of lysosomal α-Galactosidase A, which leads to the progressive accumulation of glycosphingolipids and to defective lysosomal metabolism. Currently, Fabry disease is treated by enzyme replacement therapy or the orally administrated pharmacological chaperone Migalastat. Both therapeutic strategies present limitations, since enzyme replacement therapy has shown low half-life and bioavailability, while Migalastat is only approved for patients with specific mutations. The aim of this work was to assess the efficacy of PBX galactose analogues to stabilize α-Galactosidase A and therefore evaluate their potential use in Fabry patients with mutations that are not amenable to the treatment with Migalastat. We demonstrated that PBX compounds are safe and effective concerning stabilization of α-Galactosidase A in relevant cellular models of the disease, as assessed by enzymatic activity measurements, molecular modelling, and cell viability assays. This experimental evidence suggests that PBX compounds are promising candidates for the treatment of Fabry disease caused by mutations which affect the folding of α-Galactosidase A, even for GLA variants that are not amenable to the treatment with Migalastat.

Systemic Treatment of Fabry Disease Using a Novel AAV9 Vector Expressing α-Galactosidase A.

Fabry disease is a rare X-linked disorder affecting α-galactosidase A, a rate-limiting enzyme in lysosomal catabolism of glycosphingolipids. Current treatments present important limitations, such as low half-life and limited distribution, which gene therapy can overcome. The aim of this work was to test a novel adeno-associated viral vector, serotype 9 (AAV9), ubiquitously expressing human α-galactosidase A to treat Fabry disease (scAAV9-PGK-GLA). The vector was preliminary tested in newborns of a Fabry disease mouse model. 5 months after treatment, α-galactosidase A activity was detectable in the analyzed tissues, including the central nervous system. Moreover, we tested the vector in adult animals of both sexes at two doses and disease stages (presymptomatic and symptomatic) by single intravenous injection. We found that the exogenous α-galactosidase A was active in peripheral tissues as well as the central nervous system and prevented glycosphingolipid accumulation in treated animals up to 5 months following injection. Antibodies against α-galactosidase A were produced in 9 out of 32 treated animals, although enzyme activity in tissues was not significantly affected. These results demonstrate that scAAV9-PGK-GLA can drive widespread and sustained expression of α-galactosidase A, cross the blood brain barrier after systemic delivery, and reduce pathological signs of the Fabry disease mouse model.

Bilayer Lateral Heterostructures of Transition-Metal Dichalcogenides and Their Optoelectronic Response.

Two-dimensional lateral heterojunctions based on monolayer transition-metal dichalcogenides (TMDs) have received increasing attention given that their direct band gap makes them very attractive for optoelectronic applications. Although bilayer TMDs present an indirect band gap, their electrical properties are expected to be less susceptible to ambient conditions, with higher mobilities and density of states when compared to monolayers. Bilayers and few-layers single domain devices have already demonstrated higher performance in radio frequency and photosensing applications. Despite these advantages, lateral heterostructures based on bilayer domains have been less explored. Here, we report the controlled synthesis of multi-junction bilayer lateral heterostructures based on MoS2-WS2 and MoSe2-WSe2 monodomains. The heterojunctions are created via sequential lateral edge-epitaxy that happens simultaneously in both the first and the second layers. A phenomenological mechanism is proposed to explain the growth mode with self-limited thickness that happens within a certain window of growth conditions. With respect to their as-grown monolayer counterparts, bilayer lateral heterostructures yield nearly 1 order of magnitude higher rectification currents. They also display a clear photovoltaic response, with short circuit currents ∼103 times larger than those extracted from the as-grown monolayers, in addition to room-temperature electroluminescence. The improved performance of bilayer heterostructures significantly expands the potential of two-dimensional materials for optoelectronics.

Evaluación y establecimiento de las especificaciones de calidad del pool de aceite de hígado de tiburón / Evaluation and establishment of quality specifications to pool of sharks liver oil

Objetivo: Calcular experimentalmente los límites de especificación de calidad para el pool de aceite de hígado de tiburones costeros de Cuba, a través del método de la K tabulada. Materiales y métodos: Se realizó el análisis, a diez lotes consecutivos, de los parámetros peso específico, índice de refracción, acidez, saponificación, peróxido, materia insaponificable y contenido de vitamina A y ácido palmítico. Se evaluó la distribución y la aleatoriedad de los datos y posteriormente se calcularon los límites de especificación de calidad por el método de la K tabulada, para un 95% de confianza. Resultados: Los valores obtenidos en la evaluación de los parámetros físico - químicos demostraron la calidad del aceite, cumpliendo la distribución normal y aleatoriedad de los datos, con valores de probabilidad superiores a 0,05. Conclusiones: Empleando el método de la K tabulada se establecieron límites de especificación unilaterales para el índice de acidez, contenido de vitamina A y ácido palmítico, mientras que para el peso específico, índices de refracción, saponificación, peróxido y materia insaponificable fueron bilaterales. Los lotes del pool de aceite hígado de tiburón poseen adecuada calidad, considerando los resultados de los parámetros evaluados. Se demostró que existe un alto grado de conformidad en las propiedades entre los lotes evaluados

Aims: The objective was to experimentally determine the quality specification limits for the pool of shark-liver oil from Cuban coastal sharks, by using the tabulated K method. Materials and methods: Using ten consecutive lots, an analysis was carried out of parameters such as specific weight, refractive indexes, acidity, saponification, peroxide, unsaponifiable matter, and vitamin A and palmitic acid content. The distribution and randomness of the data was assessed. Then, the quality specification limits were calculated, for a 95% degree of confidence. Results: The values obtained in the assessment of physical and chemical parameters demonstrated the quality of the oil, by adhering to the normal distribution and randomness of data, with probability values above 0,05. Conclusions: Using the tabulated K method were established unilateral quality specification limits to index of acidity and vitamin A and palmitic acid content, while to specific weight, refractive indexes, saponification, peroxide and unsaponifiable matter were bilateral. The assessed lots of pool shark-liver oil have adequate quality, considering the results of the evaluated parameters. The properties of the assessed lots showed a high degree of compliance