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The degree of π conjugation in a novel series of molecular materials containing a central oligothiophene moiety of variable length, with its end α positions capped by phenyl groups (PnTP; n = 1-4) is closely inspected by means of Fourier-transform infrared and Fourier-transform Raman spectroscopies in the neutral state as solids. Density functional theory quantum chemical calculations were performed for each co-oligomer, at the B3LYP/6-31G[sup **] level, to obtain the optimized molecular geometry and force field. The thermal stability of these oligothiophenes has been also investigated, at the molecular level, by recording infrared and Raman spectra at different temperatures between - 170 °C and 160°C. [ABSTRACT FROM AUTHOR]

Cationic solid-lipid nanoparticles (cSLNs) have become a promising tool for gene and RNA therapies. PEGylation (PEG) is crucial in enhancing particle stability and protection. We evaluated the impact of PEG on the physicochemical and biological characteristics of cholesteryl-oleate cSLNs (CO-cSLNs). Several parameters were analyzed, including the particle size, polydispersity index, zeta potential, shape, stability, cytotoxicity, and loading efficiency. Five different formulations with specific PEGs were developed and compared in both suspended and freeze-dried states. Small, homogeneous, and cationic suspended nanoparticles were obtained, with the Gelucire 50/13 (PEG-32 hydrogenated palm glycerides; Gelucire) and DSPE-mPEG2000 (1,2-distearoyl-phosphatidylethanolamine-methyl-polyethyleneglycol conjungate-2000; DSPE) formulations exhibiting the smallest particle size (~170 nm). Monodisperse populations of freeze-dried nanoparticles were also achieved, with particle sizes ranging from 200 to 300 nm and Z potential values of 30-35 mV. Notably, Gelucire again produced the smallest particle size (211.1 ± 22.4), while the DSPE and Myrj S100 (polyoxyethylene (100) stearate; PEG-100 Stearate) formulations had similar particle sizes to CO-cSLNs (~235 nm). The obtained PEGylated nanoparticles showed suitable properties: they were nontoxic, had acceptable morphology, were capable of forming SLNplexes, and were stable in both suspended and lyophilized states. These PEG-cSLNs are a potential resource for in vivo assays and have the advantage of employing cost-effective PEGs. Optimizing the lyophilization process and standardizing parameters are also recommended to maintain nanoparticle integrity.

Background: Long-term care (LTC), poverty, and socioeconomic deprivation are globally significant social issues. Ongoing population aging trends and the recent social and health emergencies caused by the COVID-19 pandemic crisis have highlighted the need for macro-level LTC and welfare system sustainability strategies., Aims: This scoping review (ScR) explores the relationship between LTC needs, the health status of older people, and the risk of socioeconomic deprivation for their households., Methods: The methodology considers different relevant sources: (a) the guidelines for ScR proposed by Lockwood et al.; (b) the recommendations of Munn et al.; (c) the PRISMA guideline for scoping reviews; and (d) the Joanna Briggs Institute (JBI) checklist. Sixty-three papers are included in the mixed-methods analysis., Results: The findings reveal the existence of a debate that seeks to understand the different characteristics of the relationship between the investigated issues. Relevant gaps in the literature are identified in terms of the concepts and approaches of the studies analyzed., Conclusions: The results indicate that the reciprocal relationship between LTC needs, supply, and the risk of socioeconomic deprivation is understudied. Future studies should focus on the causal relationship between the two phenomena and identify any internal factors that may be involved.

Type 1 diabetes (T1D) is a complex autoimmune disease that develops in genetically susceptible individuals. Most T1D-associated single nucleotide polymorphisms (SNPs) are located in non-coding regions of the human genome. Interestingly, SNPs in long non-coding RNAs (lncRNAs) may result in the disruption of their secondary structure, affecting their function, and in turn, the expression of potentially pathogenic pathways. In the present work, the function of a virus-induced T1D-associated lncRNA named ARGI (Antiviral Response Gene Inducer) is characterized. Upon a viral insult, ARGI is upregulated in the nuclei of pancreatic β cells and binds to CTCF to interact with the promoter and enhancer regions of IFNβ and interferon-stimulated genes, promoting their transcriptional activation in an allele-specific manner. The presence of the T1D risk allele in ARGI induces a change in its secondary structure. Interestingly, the T1D risk genotype induces hyperactivation of type I IFN response in pancreatic β cells, an expression signature that is present in the pancreas of T1D patients. These data shed light on the molecular mechanisms by which T1D-related SNPs in lncRNAs influence pathogenesis at the pancreatic β cell level and opens the door for the development of therapeutic strategies based on lncRNA modulation to delay or avoid pancreatic β cell inflammation in T1D., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Aims/hypothesis: Wolfram syndrome is a rare autosomal recessive disorder caused by pathogenic variants in the WFS1 gene. It is characterised by insulin-dependent diabetes mellitus, optic nerve atrophy, diabetes insipidus, hearing loss and neurodegeneration. Considering the unmet treatment need for this orphan disease, this study aimed to evaluate the therapeutic potential of glucagon-like peptide 1 receptor (GLP-1R) agonists under wolframin (WFS1) deficiency with a particular focus on human beta cells and neurons., Methods: The effect of the GLP-1R agonists dulaglutide and exenatide was examined in Wfs1 knockout mice and in an array of human preclinical models of Wolfram syndrome, including WFS1-deficient human beta cells, human induced pluripotent stem cell (iPSC)-derived beta-like cells and neurons from control individuals and individuals affected by Wolfram syndrome, and humanised mice., Results: Our study shows that the long-lasting GLP-1R agonist dulaglutide reverses impaired glucose tolerance in WFS1-deficient mice, and that exenatide and dulaglutide improve beta cell function and prevent apoptosis in different human WFS1-deficient models including iPSC-derived beta cells from people with Wolfram syndrome. Exenatide improved mitochondrial function, reduced oxidative stress and prevented apoptosis in Wolfram syndrome iPSC-derived neural precursors and cerebellar neurons., Conclusions/interpretation: Our study provides novel evidence for the beneficial effect of GLP-1R agonists on WFS1-deficient human pancreatic beta cells and neurons, suggesting that these drugs may be considered as a treatment for individuals with Wolfram syndrome., (© 2023. The Author(s).)

Objective: To review the hoaxes' characteristics spread through WhatsApp in Spain during COVID-19 lockdown and identify what kind of substances were promoted for consumption or application., Method: A phone number was activated to receive hoaxes via WhatsApp. A total of 2353 messages were collected, and among those 584 different hoaxes were identified and validated, between March 18 and April 18, 2020. From these 584 hoaxes, a sub-sample of 126 was selected, exclusively related to the object of study, and a content analysis table with fourteen registration fields was applied. Besides, the averages and medians of the quantitative fields were extracted., Results: Most of the messages received were texts (39%) and videos (30%). In the majority, the acting subject was presented as medical personnel (36.5%) or as an anonymous person (30.9%). The videos lasted between 2' 40" and 18' 18", while the audios ranged between 1' 35" and 7' 48". Regarding the gender of the informant, there was a significant difference, with 45.2% being male, and 13.5%, female and 41.3% non-identifiable., Conclusions: One out of five false health claims received was about prevention or cure of the coronavirus, based on the principle of medical authority, and basically promoting the use and consumption of substances of natural origin., (Copyright © 2020 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.)

Alternative splicing of pre-mRNA contributes strongly to the diversity of cell- and tissue-specific protein expression patterns. Global transcriptome analyses have suggested that >90% of human multiexon genes are alternatively spliced. Alterations in the splicing process cause missplicing events that lead to genetic diseases and pathologies, including various neurological disorders, cancers, and muscular dystrophies. In recent decades, research has helped to elucidate the mechanisms regulating alternative splicing and, in some cases, to reveal how dysregulation of these mechanisms leads to disease. The resulting knowledge has enabled the design of novel therapeutic strategies for correction of splicing-derived pathologies. In this review, we focus primarily on therapeutic approaches targeting splicing, and we highlight nanotechnology-based gene delivery applications that address the challenges and barriers facing nucleic acid-based therapeutics., (Copyright © 2020 Suñé-Pou, Limeres, Moreno-Castro, Hernández-Munain, Suñé-Negre, Cuestas and Suñé.)

In eukaryotes, a large amount of histones need to be synthesized during the S phase of the cell cycle to package newly synthesized DNA into chromatin. The transcription and 3' end processing of histone pre-mRNAs are controlled by the histone locus body (HLB), which is assembled on the shared promoter for H3 and H4 Here, we identified the Drosophila Prp40 pre-mRNA processing factor (dPrp40, annotated as CG3542) as a novel HLB component. We showed that dPrp40 is essential for Drosophila development, with functionally conserved activity in vertebrates and invertebrates. We observed that dPrp40 is fundamental in endocycling cells, highlighting a role for this factor in mediating replication efficiency in vivo The depletion of dPrp40 from fly cells inhibited the transcription, but not the 3' end processing, of histone mRNA in a H3 - and H4 -promoter-dependent manner. Our results establish that dPrp40 is an essential protein for Drosophila development that can localize to the HLB and might participate in histone mRNA biosynthesis., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Nanoparticle-mediated plasmid delivery is considered a useful tool to introduce foreign DNA into the cells for the purpose of DNA vaccination and/or gene therapy. Cationic solid-lipid nanoparticles (cSLNs) are considered one of the most promising non-viral vectors for nucleic acid delivery. Based on the idea that the optimization of the components is required to improve transfection efficiency, the present study aimed to formulate and characterize cholesteryl oleate-containing solid-lipid nanoparticles (CO-SLNs) incorporating protamine (P) to condense DNA to produce P:DNA:CO-SLN complexes as non-viral vectors for gene delivery with reduced cytotoxicity and high cellular uptake efficiency. For this purpose, CO-SLNs were used to prepare DNA complexes with and without protamine as DNA condenser and nuclear transfer enhancer. The main physicochemical characteristics, binding capabilities, cytotoxicity and cellular uptake of these novel CO-SLNs were analyzed. Positively charged spherical P:DNA:CO-SLN complexes with a particle size ranging from 330.1 ± 14.8 nm to 347.0 ± 18.5 nm were obtained. Positive results were obtained in the DNase I protection assay with a protective effect of the genetic material and 100% loading efficiency was achieved at a P:DNA:CO-SLN ratio of 2:1:7. Transfection studies in human embryonic kidney (HEK293T) cells showed the versatility of adding protamine to efficiently transfect cells, widening the potential applications of CO-SLN-based vectors, since the incorporation of protamine induced almost a 200-fold increase in the transfection capacity of CO-SLNs without toxicity. These results indicate that CO-SLNs with protamine are a safe and effective platform for non-viral nucleic acid delivery., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Cajal bodies are nuclear organelles involved in the nuclear phase of small nuclear ribonucleoprotein (snRNP) biogenesis. In this study, we identified the splicing factor TCERG1 as a coilin-associated factor that is essential for Cajal body integrity. Knockdown of TCERG1 disrupts the localization of the components of Cajal bodies, including coilin and NOLC1, with coilin being dispersed in the nucleoplasm into numerous small foci, without affecting speckles, gems or the histone locus body. Furthermore, the depletion of TCERG1 affects the recruitment of Sm proteins to uridine-rich small nuclear RNAs (snRNAs) to form the mature core snRNP. Taken together, the results of this study suggest that TCERG1 plays an important role in Cajal body formation and snRNP biogenesis., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)

Objective: To identify the sociodemographic profile of the homeopathy user in Spain., Design: Quantitative study., Location: Spain., Corpus: The Centre for Sociological Research database (Study 3205, February 2018), with a total of 2,486 interviews, and the sub-sample that includes all patients who have claimed to use homeopathy in Spain in the last 12 months (n=124)., Main Measurements: The percentages, means and/or standard deviation of the factors were calculated, as well as the significance of the changes in the different variables analysed in the general population, and the specific users of homeopathy in Spain. This was determined by the variance analysis or Pearson's χ 2 test, depending on the nature of the variable in the study., Results: The homeopathy user-type profile in Spain is a woman, of middle/high social status, with higher university studies, and with a progressive political ideology., Conclusions: The Spanish profile is similar to that in other international studies., (Copyright © 2018 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: To analyse the media representation of the exodus of Spanish nurses to the United Kingdom through general information newspapers., Methods: Content analysis, quantitative and qualitative. Documents published in the newspapers ABC, El País, El Mundo and La Razón, about "emigrants," "nurses" and "migrant health workers," were located from January 1, 2007, to December 31, 2016, with Boolean operators. This selected period corresponds to the beginning of the economic crisis and concludes in the year of the Brexit referendum in the United Kingdom. After applying the descriptors, 9559 texts were obtained. Once the noise of the documents was eliminated, 484 textual units were found. To carry out a more exhaustive analysis, the specific documents on "migrant nurses", which were 77, were selected and analysed qualitatively., Results: a) 2013 was the year in which the most stories about emigration in general were published, and also about nurses in particular; b) the ABC newspaper published the most stories about the exodus of nurses to the United Kingdom (31); c) El País published the most texts on Spanish emigration, with a total of 397 documents; d) 98% of the headlines analysed (n = 77) had a negative tone; and e) social discourse had greater relevance than political discourse., Conclusions: The press promoted the push factor for nurses to migrate to the United Kingdom., (Copyright © 2018 SESPAS. All rights reserved.)

Studies of the spatial organization of the highly compartmentalized eukaryotic nucleus and dynamics of transcription and RNA processing within it are fundamental for fully understanding how gene expression is regulated in the cell. Although some progress has been made in deciphering the functional consequences of this complex network of interacting molecules in the context of nuclear organization, how proteins and RNA move in the nucleus and how the transcription and RNA processing machineries find their targets are important questions that remain largely unexplored. Here, we review major hallmarks and novel insights regarding the movement of RNA and proteins in the context of nuclear organization as well as the mechanisms by which the proteins involved in RNA processing localize to specific nuclear compartments., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The tightly regulated process of precursor messenger RNA (pre-mRNA) alternative splicing (AS) is a key mechanism in the regulation of gene expression. Defects in this regulatory process affect cellular functions and are the cause of many human diseases. Recent advances in our understanding of splicing regulation have led to the development of new tools for manipulating splicing for therapeutic purposes. Several tools, including antisense oligonucleotides and trans -splicing, have been developed to target and alter splicing to correct misregulated gene expression or to modulate transcript isoform levels. At present, deregulated AS is recognized as an important area for therapeutic intervention. Here, we summarize the major hallmarks of the splicing process, the clinical implications that arise from alterations in this process, and the current tools that can be used to deliver, target, and correct deficiencies of this key pre-mRNA processing event.

Here, we present evidence for a specific role of the splicing-related factor TCERG1 in regulating apoptosis in live cells by modulating the alternative splicing of the apoptotic genes Bcl-x and Fas. We show that TCERG1 modulates Bcl-x alternative splicing during apoptosis and its activity in Bcl-x alternative splicing correlates with the induction of apoptosis, as determined by assessing dead cells, sub-G1-phase cells, annexin-V binding, cell viability, and cleavage of caspase-3 and PARP-1. Furthermore, the effect of TCERG1 on apoptosis involved changes in mitochondrial membrane permeabilization. We also found that depletion of TCERG1 reduces the expression of the activated form of the pro-apoptotic mitochondrial membrane protein Bak, which remains inactive by heterodimerizing with Bcl-xL, preventing the initial step of cytochrome c release in Bak-mediated mitochondrial apoptosis. In addition, we provide evidence that TCERG1 also participates in the death receptor-mediated apoptosis pathway. Interestingly, TCERG1 also modulates Fas/CD95 alternative splicing. We propose that TCERG1 sensitizes a cell to apoptotic agents, thus promoting apoptosis by regulating the alternative splicing of both the Bcl-x and Fas/CD95 genes. Our findings may provide a new link between the control of alternative splicing and the molecular events leading to apoptosis.