Nusinersen ameliorates motor function and prevents motoneuron Cajal body disassembly and abnormal poly(A) RNA distribution in a SMA mouse model
Artículo Materias > Biomedicina Universidad Europea del Atlántico > Investigación > Artículos y libros Abierto Inglés Spinal muscular atrophy (SMA) is a devastating autosomal recessive neuromuscular disease characterized by degeneration of spinal cord alpha motor neurons (αMNs). SMA is caused by the homozygous deletion or mutation of the survival motor neuron 1 (SMN1) gene, resulting in reduced expression of SMN protein, which leads to αMN degeneration and muscle atrophy. The majority of transcripts of a second gene (SMN2) generate an alternative spliced isoform that lacks exon 7 and produces a truncated nonfunctional form of SMN. A major function of SMN is the biogenesis of spliceosomal snRNPs, which are essential components of the pre-mRNA splicing machinery, the spliceosome. In recent years, new potential therapies have been developed to increase SMN levels, including treatment with antisense oligonucleotides (ASOs). The ASO-nusinersen (Spinraza) promotes the inclusion of exon 7 in SMN2 transcripts and notably enhances the production of full-length SMN in mouse models of SMA. In this work, we used the intracerebroventricular injection of nusinersen in the SMN∆7 mouse model of SMA to evaluate the effects of this ASO on the behavior of Cajal bodies (CBs), nuclear structures involved in spliceosomal snRNP biogenesis, and the cellular distribution of polyadenylated mRNAs in αMNs. The administration of nusinersen at postnatal day (P) 1 normalized SMN expression in the spinal cord but not in skeletal muscle, rescued the growth curve and improved motor behavior at P12 (late symptomatic stage). Importantly, this ASO recovered the number of canonical CBs in MNs, significantly reduced the abnormal accumulation of polyadenylated RNAs in nuclear granules, and normalized the expression of the pre-mRNAs encoding chondrolectin and choline acetyltransferase, two key factors for αMN homeostasis. We propose that the splicing modulatory function of nusinersen in SMA αMN is mediated by the rescue of CB biogenesis, resulting in enhanced polyadenylated pre-mRNA transcription and splicing and nuclear export of mature mRNAs for translation. Our results support that the selective restoration of SMN expression in the spinal cord has a beneficial impact not only on αMNs but also on skeletal myofibers. However, the rescue of SMN expression in muscle appears to be necessary for the complete recovery of motor function. metadata Berciano, María T.; Puente-Bedia, Alba; Medina-Samamé, Almudena; Rodríguez-Rey, José C.; Calderó, Jordi; Lafarga, Miguel y Tapia Martínez, Olga mail SIN ESPECIFICAR, SIN ESPECIFICAR, SIN ESPECIFICAR, SIN ESPECIFICAR, SIN ESPECIFICAR, SIN ESPECIFICAR, olga.tapia@uneatlantico.es (2020) Nusinersen ameliorates motor function and prevents motoneuron Cajal body disassembly and abnormal poly(A) RNA distribution in a SMA mouse model. Scientific Reports, 10 (1). ISSN 2045-2322
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Spinal muscular atrophy (SMA) is a devastating autosomal recessive neuromuscular disease characterized by degeneration of spinal cord alpha motor neurons (αMNs). SMA is caused by the homozygous deletion or mutation of the survival motor neuron 1 (SMN1) gene, resulting in reduced expression of SMN protein, which leads to αMN degeneration and muscle atrophy. The majority of transcripts of a second gene (SMN2) generate an alternative spliced isoform that lacks exon 7 and produces a truncated nonfunctional form of SMN. A major function of SMN is the biogenesis of spliceosomal snRNPs, which are essential components of the pre-mRNA splicing machinery, the spliceosome. In recent years, new potential therapies have been developed to increase SMN levels, including treatment with antisense oligonucleotides (ASOs). The ASO-nusinersen (Spinraza) promotes the inclusion of exon 7 in SMN2 transcripts and notably enhances the production of full-length SMN in mouse models of SMA. In this work, we used the intracerebroventricular injection of nusinersen in the SMN∆7 mouse model of SMA to evaluate the effects of this ASO on the behavior of Cajal bodies (CBs), nuclear structures involved in spliceosomal snRNP biogenesis, and the cellular distribution of polyadenylated mRNAs in αMNs. The administration of nusinersen at postnatal day (P) 1 normalized SMN expression in the spinal cord but not in skeletal muscle, rescued the growth curve and improved motor behavior at P12 (late symptomatic stage). Importantly, this ASO recovered the number of canonical CBs in MNs, significantly reduced the abnormal accumulation of polyadenylated RNAs in nuclear granules, and normalized the expression of the pre-mRNAs encoding chondrolectin and choline acetyltransferase, two key factors for αMN homeostasis. We propose that the splicing modulatory function of nusinersen in SMA αMN is mediated by the rescue of CB biogenesis, resulting in enhanced polyadenylated pre-mRNA transcription and splicing and nuclear export of mature mRNAs for translation. Our results support that the selective restoration of SMN expression in the spinal cord has a beneficial impact not only on αMNs but also on skeletal myofibers. However, the rescue of SMN expression in muscle appears to be necessary for the complete recovery of motor function.
| Tipo de Documento: | Artículo |
|---|---|
| Palabras Clave: | Mechanisms of disease; Neurological disorders |
| Clasificación temática: | Materias > Biomedicina |
| Divisiones: | Universidad Europea del Atlántico > Investigación > Artículos y libros |
| Depositado: | 06 Sep 2023 23:30 |
| Ultima Modificación: | 20 Mar 2025 20:06 |
| URI: | https://repositorio.uneatlantico.es/id/eprint/8684 |
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Introduction Cancer in older adults is often associated with functional limitations, geriatric syndromes, poor self-rated health, vulnerability, and frailty, and these conditions might worsen treatment-related side effects. Recent guidelines for patients with cancer during and after treatment have documented the beneficial effects of exercise to counteract certain side effects; however, little is known about the role of exercise during cancer treatment in older adults. Materials and Methods This is a multicentre randomised controlled trial in which 200 participants will be allocated to a control group or an intervention group (the sample size has been calculated to detect a clinical difference of 1 point in Short Physical Performance Battery (SPPB) score, assuming an α error of 0.05, a β error of 0.20, and a 10 % loss rate). Patients aged ≥70 years, diagnosed with any type of solid cancer and candidates for systemic treatment are eligible. Subjects in the intervention group are invited to participate in a 12-week supervised multicomponent exercise programme in addition to receiving usual care. Study assessments are conducted at baseline and three months. The primary outcome measure is physical function as assessed by the SPPB. Secondary outcome measures include comprehensive geriatric assessment scores (including social situation, basic and instrumental activities of daily living, cognitive function, depression, nutritional status, polypharmacy, geriatric syndromes, pain, and emotional distress), anthropometric characteristics, frailty status, physical fitness, physical activity, cognitive function, quality of life, fatigue, and nutritional status. Study assessments also include analysis of inflammatory, endocrine, and nutritional mediators in serum and plasma as potential frailty biomarkers at mRNA and protein levels and multiparametric flow cytometric analysis to measure immunosenescence markers on T and NK cells. Discussion This study seeks to extend our knowledge on exercise interventions during systemic anticancer treatment in patients over 70 years of age. Results from this research will guide the management of older adults during systemic treatment in hospitals seeking to enhance the standard of care.
Julia García-García mail , Ana Rodriguez-Larrad mail , Maren Martinez de Rituerto Zeberio mail , Jenifer Gómez Mediavilla mail , Borja López-San Vicente mail , Nuria Torrego Artola mail , Izaskun Zeberio Etxetxipia mail , Irati Garmendia mail , Ainhoa Alberro mail , David Otaegui mail , Francisco Borrego Rabasco mail , María M. Caffarel mail , Kalliopi Vrotsou mail , Jon Irazusta mail , Haritz Arrieta mail , Mireia Peláez mail mireia.pelaez@uneatlantico.es, Jon Belloso mail , Laura Basterretxea mail ,
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Background Post-kala-azar dermal leishmaniasis (PKDL) is a skin condition that can become a complication in about 15 % of patients who have had kala-azar. Despite its significance, treatment options for PKDL are still limited. This systematic review and meta-analysis aim to evaluate the efficacy of amphotericin B for this condition. Methods PubMed, Embase, Cochrane, and Web of Science databases were searched for randomized controlled trials (RCTs) that reported the efficacy of Liposomal Amphotericin B in the treatment of PKDL. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Events per 100 observations with 95 % confidence intervals were performed for outcomes. Results Nine studies with 639 patients were included, the treatment durations ranging from 7 to 60 days. The mean age ranged from 9.2 to 31.0 years, and 359 patients were male. The PKDL treatment with liposomal amphotericin B resulted in a cure rate of 91.36 % (95 % CI: 76.60-97.15). However, a relapse was observed in 11.42 % (95 % CI: 6.20-20.8) of patients. Adverse events were common, with hepatic enzyme elevation (ALT/AST) being the most frequent (61.75 %; 95 % CI: 21.81–90.33), followed by fever in 29.93 % of cases (95 % CI: 5.09–77.30). Among the more serious side effects, decreased serum potassium was observed in 19.27 % (95 % CI: 3.84–58.82), and increased serum creatinine, indicative of nephrotoxicity, occurred in 15.08 % (95 % CI: 3.97–43.27). Nausea or vomiting, although less severe, affected 12.36 % of patients (95 % CI: 4.81–28.25). Conclusions These findings highlight that while liposomal amphotericin B is a potent therapeutic option for PKDL, its administration requires careful management and clinical vigilance to optimize outcomes and minimize risks.
Deivyd Vieira Silva Cavalcante mail , Lilia Maria Lima de Oliveira mail , Noor Husain mail , Beatriz Ximenes Mendes mail , Ana Clara Felix de Farias Santos mail , Luciana Borrigueiro mail , Lyria de Oliveira Rosa mail , Christian Ndikuryayo mail , Sarah Soares Amorim mail , Lalit Mohan mail , Fabiana Castro Porto Silva Lopes mail ,
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Background/Objectives: The growing integration of Artificial Intelligence (AI) and chatbots in health professional education offers innovative methods to enhance learning and clinical preparedness. This study aimed to evaluate the educational impact and perceptions in university students of Human Nutrition and Dietetics, regarding the utility, usability, and design of the E+DIEting_Lab chatbot platform when implemented in clinical nutrition training. Methods: The platform was piloted from December 2023 to April 2025 involving 475 students from multiple European universities. While all 475 students completed the initial survey, 305 finished the follow-up evaluation, representing a 36% attrition rate. Participants completed surveys before and after interacting with the chatbots, assessing prior experience, knowledge, skills, and attitudes. Data were analyzed using descriptive statistics and independent samples t-tests to compare pre- and post-intervention perceptions. Results: A total of 475 university students completed the initial survey and 305 the final evaluation. Most university students were females (75.4%), with representation from six languages and diverse institutions. Students reported clear perceived learning gains: 79.7% reported updated practical skills in clinical dietetics and communication were updated, 90% felt that new digital tools improved classroom practice, and 73.9% reported enhanced interpersonal skills. Self-rated competence in using chatbots as learning tools increased significantly, with mean knowledge scores rising from 2.32 to 2.66 and skills from 2.39 to 2.79 on a 0–5 Likert scale (p < 0.001 for both). Perceived effectiveness and usefulness of chatbots as self-learning tools remained positive but showed a small decline after use (effectiveness from 3.63 to 3.42; usefulness from 3.63 to 3.45), suggesting that hands-on experience refined, but did not diminish, students’ overall favorable views of the platform. Conclusions: The implementation and pilot evaluation of the E+DIEting_Lab self-learning virtual patient chatbot platform demonstrate that structured digital simulation tools can significantly improve perceived clinical nutrition competences. These findings support chatbot adoption in dietetics curricula and inform future digital education innovations.
Iñaki Elío Pascual mail inaki.elio@uneatlantico.es, Kilian Tutusaus mail kilian.tutusaus@uneatlantico.es, Imanol Eguren García mail imanol.eguren@uneatlantico.es, Álvaro Lasarte García mail , Arturo Ortega-Mansilla mail arturo.ortega@uneatlantico.es, Thomas Prola mail thomas.prola@uneatlantico.es, Sandra Sumalla Cano mail sandra.sumalla@uneatlantico.es,
Elío Pascual
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Objective: Children’s dietary choices are influenced by several factors, including parents’ modeling. The relation between parents’ psychosocial factors and their children’s level of adherence to the Mediterranean diet were explored. Methods: Food literacy, perceived barriers and enablers, and healthy-eating attitude following the Capability, Opportunity and Motivation (COM-B) model for behavioral change were evaluated in 2,011 participants in the DELICIOUS (UnDErstanding consumer food choices & promotion of healthy and sustainable Mediterranean Diet and LIfestyle in Children and adolescents through behavIOUral change actionS) project. Adherence to the Mediterranean diet was assessed through the KIDMED questionnaire. Beta coefficients and standard errors (SEs) were calculated through linear regression analyses. Results: Post-adjustment for potential confounding factors, results showed significant positive correlation between children’s adherence to the Mediterranean diet and parental food literacy [β (SE) = 0.180 (0.011)], perceived barriers and enablers [β (SE) = 0.135 (0.009)], and healthy-eating attitudes (divided into five constructs) [β (SE) = 0.069 (0.030), β (SE) = 0.037 (0.029), β (SE) = 0.162 (0.017), β (SE) = 0.147 (0.010), β (SE) = 0.158 (0.011)]. Individual dietary components of the Mediterranean diet were also associated with various psychosocial factors. Conclusion: These results confirm the importance of parental food literacy, perceived enablers and barriers to healthy-eating, health-eating attitude in their children’s adherence to the Mediterranean diet.
Sabrina Castellano mail , Wen Rui Choo mail , Alice Rosi mail , Tania Abril Mera mail , Francesca Scazzina mail , Francesca Giampieri mail francesca.giampieri@uneatlantico.es, Evelyn Frias-Toral mail , Osama Abdelkarim mail , Mohamed Aly mail , Achraf Ammar mail , Juancho Pons mail , Laura Vázquez-Araújo mail , Fernando Maniega Legarda mail , Lorenzo Monasta mail , Alessandro Scuderi mail , Nunzia Decembrino mail , Ana Mata mail , Adrián Chacón mail , Pablo Busó mail , Giuseppe Grosso mail ,
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Enzymatic treatment shapes in vitro digestion pattern of phenolic compounds in mulberry juice
The health benefits of mulberry fruit are closely associated with its phenolic compounds. However, the effects of enzymatic treatments on the digestion patterns of these compounds in mulberry juice remain largely unknown. This study investigated the impact of pectinase (PE), pectin lyase (PL), and cellulase (CE) on the release of phenolic compounds in whole mulberry juice. The digestion patterns were further evaluated using an in vitro simulated digestion model. The results revealed that PE significantly increased chlorogenic acid content by 77.8 %, PL enhanced cyanidin-3-O-glucoside by 20.5 %, and CE boosted quercetin by 44.5 %. Following in vitro digestion, the phenolic compound levels decreased differently depending on the treatment, while cyanidin-3-O-rutinoside content increased across all groups. In conclusion, the selected enzymes effectively promoted the release of phenolic compounds in mulberry juice. However, during gastrointestinal digestion, the degradation of phenolic compounds surpassed their enhanced release, with effects varying based on the compound's structure.
Peihuan Luo mail , Jian Ai mail , Qiongyao Wang mail , Yihang Lou mail , Zhiwei Liao mail , Francesca Giampieri mail francesca.giampieri@uneatlantico.es, Maurizio Battino mail maurizio.battino@uneatlantico.es, Elwira Sieniawska mail , Weibin Bai mail , Lingmin Tian mail ,
Luo