Intracellular pathways involved in cell survival are deregulated in mouse and human spinal muscular atrophy motoneurons

Spinal Muscular Atrophy (SMA) is a severe neuromuscular disorder caused by loss of the Survival Motor Neuron 1 gene (SMN1). Due to this depletion of the survival motor neuron (SMN) protein, the disease is characterized by the degeneration of spinal cord motoneurons (MNs), progressive muscular atrophy, and weakness. Nevertheless, the ultimate cellular and molecular mechanisms leading to cell loss in SMN-reduced MNs are only partially known. We have investigated the activation of apoptotic and neuronal survival pathways in several models of SMA cells. Even though the antiapoptotic proteins FAIM-L and XIAP were increased in SMA MNs, the apoptosis executioner cleaved-caspase-3 was also elevated in these cells, suggesting the activation of the apoptosis process. Analysis of the survival pathway PI3K/Akt showed that Akt phosphorylation was reduced in SMA MNs and pharmacological inhibition of PI3K diminished SMN and Gemin2 at transcriptional level in control MNs. In contrast, ERK phosphorylation was increased in cultured mouse and human SMA MNs. Our observations suggest that apoptosis is activated in SMA MNs and that Akt phosphorylation reduction may control cell degeneration, thereby regulating the transcription of Smn and other genes related to SMN function.This work was supported by grants from Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias, Unión Europea, Fondo Europeo de Desarrollo Regional (FEDER) “Una manera de hacer Europa” (PI17/00231 and PI20/00098) to RMS and AG; CERCA Program/Generalitat de Catalunya; and Spanish Agency of Research (Agencia Estatal de Investigacion-PID2019- 107286RB-I00) and CIBERNED to JXC. AS holds a fellowship from Universitat de Lleida and SdF holds a fellowship from “Ajuts de Promoció de la Recerca en Salut” (IRBLleida-Diputació de Lleida). We thank Elaine Lilly, PhD, for English language revision of the paper

Plasma irisin depletion under energy restriction is associated with improvements in lipid profile in metabolic syndrome patients

OBJECTIVE: A recently discovered myokine, irisin, may have an important role in energy metabolism. This study aimed to evaluate the relationship between this hormone and the lipid profile of patients with metabolic syndrome (MetS) following a hypocaloric diet. DESIGN: Ninety-three Caucasian adults (52 men/41 women) diagnosed with MetS followed an 8-week-long energy-restricted programme (-30% of the energy requirements). Anthropometric measurements, biochemical markers and plasma irisin levels were analysed before and after the nutritional intervention. RESULTS: Global plasma irisin levels were significantly reduced at the end of the study (-72.0 +/- 100.9 ng/ml, P < 0.001) accompanying the weight loss (-6.9%). The depletion of irisin significantly correlated with changes in some atherogenic-related variables: total cholesterol (B = 0.106, P = 0.018), total cholesterol/high-density lipoprotein cholesterol ratio (B = 0.002, P = 0.036), low-density lipoprotein cholesterol (B = 0.085, P = 0.037) and apolipoprotein B (B = 0.052, P = 0.002), independently of changes in body weight. CONCLUSIONS: An association between the reduction in plasma irisin levels and the depletion of important lipid metabolism biomarkers was observed in patients with MetS undergoing an energy-restricted programme

Molecular and biochemical characterization of extracellular tannin acyl hydrolase activity from a Mexican isolate of Aspergillus niger

"Microbial tannase, a hydrolysable tannin-degrading enzyme, is extensively used in manufacture of instant tea, beer, wine, and gallic acid. Aspergillus niger strain, obtained from a Mexican tannery wastewaters rich in gallic acid [Quebracho Phenolics-rich Tannery Wastewaters, (QPTW)], displayed a good growth and tannase activity in a minimal medium added with 1% (w/v) QPTW (Kr= 0.451 mm.h-1). Using PCR and RACE 3´ and 5´methodologies, a complete cDNA of a tannase was cloned from this isolate.Nucleotide sequence of complete cDNA was of 4690 bp with a complete ORF of 1833 bp encoding 611 amino acids. Transcriptionalinduction was observed in mineral medium added with carbon sources as tannic acid alone (1 and 10 g/l), as well as mix of glucose(1 and 10 g/l) and tannic acid (1 g/l) in the media. However, neither glucose (1 and 10 g/l) and sucrose (1 and 10 g/l) nor (+)-catechin(1 and 10 g/l) as sole carbon sources displayed gene induction in in vitro assays. A. niger-GTO is a new strain with interesting characteristics for industrial tannase production purposes.

Diet Supplementation with Polyphenol-Rich Salicornia ramosissima Extracts Protects against Tissue Damage in Experimental Models of Cerebral Ischemia

Salicornia; Ischemia; NeuroprotectionSalicornia; Isquemia; NeuroprotecciónSalicornia; Isquèmia; NeuroproteccióStrokes are the second most common cause of death worldwide and a leading cause of disability. Regular consumption of polyphenols has been shown to reduce the risk of suffering a cardiovascular event. For this reason, we have investigated the protective effect of Salicornia ramosissima, a seasonal halophyte that synthetizes high amounts of bioactive compounds, including polyphenols, in response to environmental stress. Aqueous, hydroalcoholic, and ethanolic extracts were prepared to investigate if dietary supplementation prior to ischemic challenge can prevent subsequent damage using two animal models. First, we screened the protective effect against hypoxia–reoxygenation in Drosophila melanogaster and observed that both ethanolic and hydroalcoholic extracts protected flies from the deleterious effects of hypoxia. Second, we confirmed the protective effect of S. ramosissima ethanolic extract against brain ischemia using the transient middle cerebral artery occlusion mice model. Four weeks of oral supplementation with the ethanolic extract before artery occlusion reduced infarct volume and lowered the plasma levels of the DNA peroxidant product 8-hydroxydeoxyguanosine. Phytochemical profiling of S. ramosissima ethanolic extract revealed 50 compounds. Thus, it represents a valuable source of bioactive compounds that show promising disease-modifying activities and could be further developed as an effective food supplement for the prevention or treatment of neurovascular disorders.The authors received financial support from “CSF-Proyectos estratégicos de I+D+i. Proyectos cofinanciados en un 80% por fondos del Programa Operativo FEDER de Andalucía 2014–2020”, grant number PE-0527-2019. This research was partially funded by “Consejería de Transformación Económica, Industria, Conocimiento y Universidades (CTEICU) y 80% cofinanciados por la UE, PO FEDER Andalucía 2014-2020”, grant number [PY20_01351]. C.d.R. received financial support from the Sara Borrell program funded by ISCIII, grant number [CD21/00148]

HLA-C genotype and TCR vβ expression analysis in Mexican patients with Psoriasis

"Genetic background and T-cell expansion have been associated as the most important factors for psoriasis susceptibility in the Caucasian population. This study was performed to identify the T cell receptor Vβ repertoire and HLA-Cw genotype in two Mexican groups with severe chronic plaque-type psoriasis. HLA-C typing was performed to detect the allele pattern associated with the disease by sequence-specific primer-polymerase chain reaction. In parallel, RT-PCR and Western blot were used for the identification of the TCR Vβ repertoire. We found a wide variety of HLA-C alleles displayed with a preference to HLA-Cw *07 as the most representative allele in the group of patients. TCR Vβ-2 and Vβ-7 clone-type frequencies were statistically significant (p of 0.0280) when compared to other TCR Vβ expressed in the two groups. We found notable differences both in the HLA-C genotype and TCR Vβ repertoire in the groups of patients studied. Since Mexican individuals are genetically different from the Caucasian population, we suggest that due to these differences the susceptibility to disease and activation of T-cells for a proper immune response may be affected.

Effectiveness of antitussives, anticholinergics or honey versus usual care in adults with uncomplicated acute bronchitis: a study protocol of an open randomised clinical trial in primary care

Introduction: Despite the frequent use of therapies in acute bronchitis, the evidence of their benefit is lacking, since only a few clinical trials have been published, with low sample sizes, poor methodological quality and mainly in children. The objective of this study is to compare the effectiveness of three symptomatic therapies (dextromethorphan, ipratropium or honey) associated with usual care and the usual care in adults with acute bronchitis. Methods and analysis: This will be a multicentre, pragmatic, parallel group, open randomised trial. Patients aged 18 or over with uncomplicated acute bronchitis, with cough for less than 3 weeks as the main symptom, scoring ≥4 in either daytime or nocturnal cough on a 7-point Likert scale, will be randomised to one of the following four groups: usual care, dextromethorphan 30 mg three times a day, ipratropium bromide inhaler 20 µg two puffs three times a day or honey 30 mg (a spoonful) three times a day, all taken for up to 14 days. The exclusion criteria will be pneumonia, criteria for hospital admission, pregnancy or lactation, concomitant pulmonary disease, associated significant comorbidity, allergy, intolerance or contraindication to any of the study drugs or admitted to a long-term residence. Sample: 668 patients. The primary outcome will be the number of days with moderate-to-severe cough. All patients will be given a paper-based symptom diary to be self-administered. A second visit will be scheduled at day 2 or 3 for assessing evolution, with two more visits at days 15 and 29 for clinical assessment, evaluation of adverse effects, re-attendance and complications. Patients still with symptoms at day 29 will be called 6 weeks after the baseline visit. Ethics and dissemination: The study has been approved by the Ethical Board of IDIAP Jordi Gol (reference number: AC18/002). The findings of this trial will be disseminated through research conferences and peer-review journals. Trial registration: number NCT03738917; Pre-results

Debate sobre la Ley Federal del Trabajo

Se recuerda con preocupación la forma como la política laboral instrumentada en el sexenio de Carlos Salinas impuso "soluciones" a cada uno de los conflictos obrero patronales, soluciones adoptadas al margen y por sobre la normatividad laboral de esos días. Se abre boca a la discusión sin pensar que los avances tengan alguna significación, ya que muy pronto se llegó a ciertas conclusiones colectivas, de definición y proposición de temáticas tales como la libertad sindical, las condiciones de trabajo y la efectividad de las nuevas normas. Estas propuestas y reflexiones hechas en un contexto en el que la productividad en el trabajo y la capacitación para su realización, son preocupaciones de los trabajadores y sus sindicatos, en que la búsqueda de una salida a la crisis económica que padecemos puede ser encontrada sin mayores sacrificios que los que ya padece la clase trabajadora y en función a un interés nacional y popular