Catalytic Diastereo- and Enantioselective Vinylogous Mannich Reaction of Alkylidenepyrazolones to Isatin-Derived Ketimines

[EN] A valuable organocatalytic vinylogous Mannich reaction between alkylidenepyrazolones and isatin-derived ketimines has been successfully established. Squaramide organocatalyst, prepared from quinine, catalyzed the diastereo- and enantioselective vinylogous Mannich addition, affording a range of aminooxindole-pyrazolone adducts (24 examples) with excellent outcomes: up to 98% yield with complete diastereoselectivity and excellent enantioselectivity (up to 99% ee). Additionally, different synthetic transformations were performed with the chiral pyrazolone-oxindole adducts.Financial support from the Agencia Estatal de Investigacion (AEI, Spanish Government) and Fondo Europeo de Desarrollo Regional (FEDER, European Union) (PID2020-116944GB) and from Conselleria d'Innovacio, Universitat, Ciencia i Societat Digital (AICO/2020/68) is acknowledged. L.C.-F. thanks the Universitat de Valencia for a predoctoral grant. C.V. thanks the Spanish Government for a RyC contract (RYC2016-20187). Access to the NMR, MS, and X-ray facilities from the Servei Central de Suport a la Investigacio Experimental (SCSIE)-UV is also acknowledged.Carceller-Ferrer, L.; Vila, C.; Blay, G.; Muñoz Roca, MDC.; Pedro, JR. (2021). Catalytic Diastereo- and Enantioselective Vinylogous Mannich Reaction of Alkylidenepyrazolones to Isatin-Derived Ketimines. Organic Letters. 23(19):7391-7395. https://doi.org/10.1021/acs.orglett.1c0257173917395231

The hippocampus as the switchboard between perception and memory.

Adaptive memory recall requires a rapid and flexible switch from external perceptual reminders to internal mnemonic representations. However, owing to the limited temporal or spatial resolution of brain imaging modalities used in isolation, the hippocampal–cortical dynamics supporting this process remain unknown. We thus employed an object-scene cued recall paradigm across two studies, including intracranial electroencephalography (iEEG) and high-density scalp EEG. First, a sustained increase in hippocampal high gamma power (55 to 110 Hz) emerged 500 ms after cue onset and distinguished successful vs. unsuccessful recall. This increase in gamma power for successful recall was followed by a decrease in hippocampal alpha power (8 to 12 Hz). Intriguingly, the hippocampal gamma power increase marked the moment at which extrahippocampal activation patterns shifted from perceptual cue toward mnemonic target representations. In parallel, source-localized EEG alpha power revealed that the recall signal progresses from hippocampus to posterior parietal cortex and then to medial prefrontal cortex. Together, these results identify the hippocampus as the switchboard between perception and memory and elucidate the ensuing hippocampal–cortical dynamics supporting the recall process.post-print1844 K

Ahora / Ara

La cinquena edició del microrelatari per l’eradicació de la violència contra les dones de l’Institut Universitari d’Estudis Feministes i de Gènere «Purificación Escribano» de la Universitat Jaume I vol ser una declaració d’esperança. Aquest és el moment en el qual les dones (i els homes) hem de fer un pas endavant i eliminar la violència sistèmica contra les dones. Ara és el moment de denunciar el masclisme i els micromasclismes començant a construir una societat més igualitària. Cadascun dels relats del llibre és una denúncia i una declaració que ens encamina cap a un món millor

Extracellular Vesicles Do Not Mediate the Anti-Inflammatory Actions of Mouse-Derived Adipose Tissue Mesenchymal Stem Cells Secretome

Adipose tissue represents an abundant source of mesenchymal stem cells (MSC) for therapeutic purposes. Previous studies have demonstrated the anti-inflammatory potential of adipose tissue-derived MSC (ASC). Extracellular vesicles (EV) present in the conditioned medium (CM) have been shown to mediate the cytoprotective effects of human ASC secretome. Nevertheless, the role of EV in the anti-inflammatory effects of mouse-derived ASC is not known. The current study has investigated the influence of mouse-derived ASC CM and its fractions on the response of mouse-derived peritoneal macrophages against lipopolysaccharide (LPS). CM and its soluble fraction reduced the release of pro-inflammatory cytokines, adenosine triphosphate and nitric oxide in stimulated cells. They also enhanced the migration of neutrophils or monocytes, in the absence or presence of LPS, respectively, which is likely related to the presence of chemokines, and reduced the phagocytic response. The anti-inflammatory effect of CM may be dependent on the regulation of toll-like receptor 4 expression and nuclear factor-κB activation. Our results demonstrate the anti-inflammatory effects of mouse-derived ASC secretome in mouse-derived peritoneal macrophages stimulated with LPS and show that they are not mediated by EV

Extracellular Vesicles Do Not Mediate the Anti-Inflammatory Actions of Mouse-Derived Adipose Tissue Mesenchymal Stem Cells Secretome

Adipose tissue represents an abundant source of mesenchymal stem cells (MSC) for therapeutic purposes. Previous studies have demonstrated the anti-inflammatory potential of adipose tissue-derived MSC (ASC). Extracellular vesicles (EV) present in the conditioned medium (CM) have been shown to mediate the cytoprotective effects of human ASC secretome. Nevertheless, the role of EV in the anti-inflammatory effects of mouse-derived ASC is not known. The current study has investigated the influence of mouse-derived ASC CM and its fractions on the response of mouse-derived peritoneal macrophages against lipopolysaccharide (LPS). CM and its soluble fraction reduced the release of pro-inflammatory cytokines, adenosine triphosphate and nitric oxide in stimulated cells. They also enhanced the migration of neutrophils or monocytes, in the absence or presence of LPS, respectively, which is likely related to the presence of chemokines, and reduced the phagocytic response. The anti-inflammatory effect of CM may be dependent on the regulation of toll-like receptor 4 expression and nuclear factor-κB activation. Our results demonstrate the anti-inflammatory effects of mouse-derived ASC secretome in mouse-derived peritoneal macrophages stimulated with LPS and show that they are not mediated by EV

Efficacy of stem cells in bone rehabilitation in patients with alveolar bone atrophy: a systematic review

Background: Biomedical engineering proposes the use of stem cells as a bone rehabilitation treatment in patients with alveolar bone defects. Many authors suggest that this innovative technique could represent the future of bone regeneration in dentistry. The present study systematically reviewed the efficacy of stem cells in bone regeneration in patients with alveolar bone atrophy. Material and methods: The study was developed following the criteria of the PRISMA guideline (2020). The literature review was conducted in Pubmed, Medline Complete, and Scopus. The search algorithms used the following key words: stem cells, bone regeneration, and alveolar ridge augmentation. To assess the risk of bias, the CASPe methodology was used. Results: Seven clinical trials in humans were included in this systematic review. In all the studies, the proposed objective of bone regeneration by using stem cells was achieved, although in a different way with different results. Although the authors of the analysed clinical trials achieved favourable results, they highlighted the presence of multiple limitations throughout bone regeneration treatments, such as scarce scientific literature on stem cells, a reduced number of follow-up studies, and a lack of a standardized international protocol. Conclusions: Based on the analysed studies, it is concluded that the therapy proposed by tissue engineering through the use of stem cells to rehabilitate patients with bone atrophies can be considered effective. In addition, the need for further studies and standardization of protocols is highlighted.Sin financiación2.883 JCR (2021) Q2, 46/92 Dentistry, Oral Science & Medicine0.681 SJR (2021) Q1, 30/142 Dentistry (miscellaneous)No data IDR 2021UE

Chondroprotective effects of the combination chondroitin sulfate-glucosamine in a model of osteoarthritis induced by anterior cruciate ligament transection in ovariectomised rats

[EN] Context: The efficacy of the combination chondroitin sulfate-glucosamine (CS-GlcN) in the treatment of knee osteoarthritis (OA) has been suggested in recent clinical studies. In vitro reports have also suggested anti-inflammatory and anti-resorptive effects of this combination. Objective: The aim of this study was to characterize the effects of CS-GlcN on joint degradation in vivo including the assessment of inflammation and bone metabolism in a model of OA. Materials and methods: We have used the OA model induced by anterior cruciate ligament transection (ACLT) in ovariectomised rats. CS-GlcN was administered daily (oral gavage) from week 0 until week 12 after ovariectomy at the dose of 140 (CS) + 175 (GlcN)(HCl) mg/kg. Histochemical analyses were performed, the levels of biomarkers and inflammatory mediators were measured by luminex or ELISA and bone microstructure was determined by mCT. Results: CS-GlcN protected against cartilage degradation and reduced the levels of inflammatory mediators such as interleukin-1b and tumor necrosis factor-a in the affected knee. In addition, serum biomarkers of inflammation and cartilage and bone degradation including matrix metalloproteinase-3, C-telopeptide of type II collagen and the ratio receptor activator of nuclear factor kB ligand/ osteoprotegerin were significantly decreased by CS-GlcN. This treatment also tended to improve some bone microstructural parameters without reaching statistical significance. Discussion and conclusions: These results demonstrate the chondroprotective effects of CS-GlcN in vivo, in the experimental model of ACLT in ovariectomised rats, and suggest that this combination may be useful to control the joint catabolic effects of inflammatory stress. These findings could have clinical relevance related to the prevention of joint degradation by CS-GlcN and support the potential development of OA treatments based on this combination.The authors thank Ms. Anna Blanco for her technical assistance. The present study was supported by grants from Bioiberica S.A. and Spanish Ministerio de Economia y Competitividad, ISCIII, FEDER (RETICEF RD12/0043/0013). The funding sources had no role in the conduct of the study; collection, management, analysis, interpretation of the data; and preparation of the manuscript. A.T., P.D., R.R., E.M. and J.V. are employed by Bioiberica S.A.Terencio, MC.; Ferrandiz, ML.; Carceller, C.; Ruhi, R.; Dalmau, P.; Verges, J.; Montell, E.... (2016). Chondroprotective effects of the combination chondroitin sulfate-glucosamine in a model of osteoarthritis induced by anterior cruciate ligament transection in ovariectomised rats. Biomedicine & Pharmacotherapy. 79:120-128. https://doi.org/10.1016/j.biopha.2016.02.0051201287

Estudio del transporte mucociliar y de la ultraestructura ciliar nasales en pacientes con síndrome de Kartagener

Objetivo: El síndrome de Kartagener (SK) es una variante clínica de la discinesia ciliar primaria que asocia a las infecciones crónicas de las vías respiratorias un situs inversus. La ausencia de brazos de dineína ha sido el defecto ciliar asociado a este síndrome. El objeto de este trabajo es el estudio del transporte mucociliar y de la ultraestructura ciliar en 14 pacientes con SK. Pacientes y métodos: Hemos estudiado el transporte mucociliar nasal, mediante una técnica radioisotópica, y la ultraestructura ciliar en 14 pacientes con SK. Resultados: En 13 pacientes había estasis mucociliar y en uno, un transporte muy enlentecido (1,3 mm/min). Mostraban cilios con brazos de dineína normales 4 pacientes (29%); brazos internos de dineína cortos, 2 pacientes (14%), y ausencia completa de brazos internos y externos de dineína, 8 casos (57,1%). Conclusiones: Concluimos que la presentación clínica típica junto con un transporte mucociliar alterado, objetivado con una técnica isotópica, es diagnóstica del SK, aunque la ultraestructura ciliar sea normal. El SK es clínicamente homogéneo y morfológicamente heterogéneo