Intolerance of uncertainty, rumination, post-traumatic stress symptoms and aggression during COVID-19: a serial mediation model.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic can be identified as a source of traumatic stress. Previous studies have shown that post-traumatic stress and intolerance of uncertainty are associated with aggressive behaviour. OBJECTIVE: In the present study, we aimed to test a serial mediation model, considering rumination and post-traumatic stress symptoms (PTSS) as mediators that link intolerance of uncertainty and aggression, while controlling the confounding effect of crisis-induced health and socioeconomic stressors during the COVID-19 pandemic. METHOD: A total of 714 participants [533 (74.6%) females, 176 (24.7%) males, aged 18-64 years (M age = 25.16, SD age = 9.34)] completed the following self-reported scales: Aggression Scale, COVID-19 stressors checklist, Short Version of the Intolerance of Uncertainty Scale, Impact of Event Scale with Modifications for COVID-19, and Ruminative Thought Style Questionnaire. RESULTS: The results revealed that there was an association between intolerance of uncertainty and aggressive behaviours. Moreover, the results of serial mediation analysis showed that intolerance of uncertainty predicts aggressive behaviours via rumination and PTSS. Besides, socioeconomic stressors are significantly associated with the level of PTSS and aggression, while health stressors are not significantly association with the level of PTSS and aggression. CONCLUSIONS: The findings provide several contributions to understand the link between intolerance of uncertainty and aggressive behaviours during the COVID-19 pandemic, and confirm the importance of early psychological intervention, especially for those who are more likely to ruminate and suffer from PTSS, to prevent aggression and violence in the long run. In addition to health-related regulations, it is important to take the social and economic aspects of the crisis into account and develop intervention strategies accordingly. Nevertheless, the limitations of cross-sectional mediation analysis in explaining causal relationships should be kept in mind, and future studies should extend these findings using longitudinal data.

Antecedentes: La pandemia por COVID-19 se puede identificar como una fuente de estrés traumático, y estudios previos mostraron que el estrés postraumático y la intolerancia a la incertidumbre están asociados con el comportamiento agresivo.Objetivo: En el presente estudio, nuestro objetivo fue probar un modelo de mediación en serie, considerando la rumiación y los síntomas de estrés postraumático (SEPT) como mediadores que vinculan la intolerancia a la incertidumbre y la agresión, controlando el efecto de confusión de los factores estresantes socioeconómicos y de salud inducidos por crisis durante la pandemia de COVID-19.Método: Un total de 714 participantes (533 [74,6%] mujeres, 176 [24,7%] hombres de entre 18 y 64 años (Medad = 25.16, DEedad = 9.34) completaron las siguientes escalas de auto-reporte: Escala de agresión, Lista de Chequeo de Factores Estresantes por COVID-19, Versión Corta de la Escala de Intolerancia a la incertidumbre, Escala de Impacto de Eventos con modificaciones para COVID-19 y Cuestionario de Estilo de Pensamiento Rumiante.Resultados: Los resultados revelaron una asociación entre la intolerancia a la incertidumbre y las conductas agresivas. Además, el resultado del análisis de mediación en serie mostró que la intolerancia a la incertidumbre predice comportamientos agresivos a través de la rumiación y los SEPT. Además, los factores de estrés socioeconómico están significativamente asociados con el nivel de SEPT y la agresión, mientras que los estresores de salud no están significativamente asociados con el nivel de SEPT y la agresión.Conclusiones: Los hallazgos brindan varias contribuciones para comprender el vínculo entre la intolerancia a la incertidumbre y los comportamientos agresivos durante la pandemia de COVID-19 y la importancia de la intervención psicológica temprana, especialmente para aquellos que tienen más probabilidades de presentar rumiación y sufrir SEPT para prevenir la agresión y la violencia a largo plazo. Además de las regulaciones relacionadas con la salud, es importante tener en cuenta los aspectos sociales y económicos de las crisis, y desarrollar en concordancia estrategias de intervención. No obstante, deben tenerse en cuenta las limitaciones del análisis de mediación transversal para explicar las relaciones causales y los estudios futuros deben ampliar los hallazgos mediante el uso de datos longitudinales.

BSA and fibrinogen adsorption on chitosan/κ-carrageenan polyelectrolyte complexes.

PECs of chitosan/κ-carrageenan are prepared in three different volumetric rations. The complex formation is characterized in order to evaluate the blending formation. Blood compatibility is evaluated by protein adsorption (BSA and fibrinogen) and PEC toxicities are determined with fibroblast cell viability and proliferation. The swelling degree of PECs decreases when the amount of chitosan increases. Due to the linked film formation, PECs decrease BSA adsorption and increase fibrinogen adsorption when compared to the pristine chitosan and κ-carrageenan films. Although pristine chitosan and κ-carrageenan films produced similar cell expansion and viability, the PEC 50:50 vol% chitosan/κ-carrageenan PEC may be acceptable as a new scaffold for cell therapies, due to their effect on cell survival.

Human elastin-based recombinant biopolymers improve mesenchymal stem cell differentiation.

Elastin-based polypeptides are a class of smart biopolymers representing an important model in the design of biomaterials. The combination of biomimetic materials with cells that have great plasticity provides a promising strategy for the realization of highly engineered cell-based constructs for regenerative medicine and tissue repair applications. Two recombinant biopolymers inspired by human elastin are assessed as coating agents to prepare biomimetic surfaces for cell culture. These substrates are assayed for hBM MSC culture. The coated surfaces are also characterized with AFM to evaluate the topographical features of the deposited biopolymers. The results suggest that the elastin-derived biomimetic surfaces play a stimulatory role on osteogenic differentiation of MSCs.

Insulin-like growth factor binding protein-2 and neurotrophin 3 synergize together to promote the expansion of hematopoietic cells ex vivo.

Co-culture of Umbilical Cord Blood (UCB) CD34+ cells with irradiated Mesenchymal Stem Cells (MSCs) without contact increase the expansion of Hematopoietic Progenitor Cells (HPC). Neurotrophin-3 (NT-3) and insulin-like growth factor binding protein-2 (IGFBP-2) are two factors whose expressions were significantly elevated in conditioned media derived from irradiated MSCs. To determine whether these factors are partly responsible for the growth promoting potential of MSCs, we investigated their impact on the growth and differentiation of UCB-CD34+ cells. Addition of either factor alone had little impact on cell growth, however both factors synergized together to increase the expansion of total nucleated cells, erythroids, megakaryocytes (Mk) and CD34+ cells. However, in contrast to MSCs they failed to significantly improve the expansion of hematopoietic progenitors. Consistent with the impact of these factors on hematopoietic cells, both synergized to activate ERK1/2 and AKT in primary human UCB cells. In conclusion, the study demonstrates for the first time that a neurotrophin factor can synergize with IGFBP-2 to promote hematopoietic cell expansion.

Effects of extracellular matrix proteins on the growth of haematopoietic progenitor cells.

Umbilical cord blood (UCB) transplantation and haematological recovery are currently limited by the amount of haematopoietic progenitor cells (HPCs) present in each unit. HPCs and haematopoietic stem cells (HSCs) normally interact with cells and extracellular matrix (ECM) proteins present within the endosteal and vascular niches. Hence, we investigated whether coating of culture surfaces with ECM proteins normally present in the marrow microenvironment could benefit the ex vivo expansion of HPCs. Towards this, collagen types I and IV (COL I and IV), laminin (LN) and fibronectin (FN) were tested individually or as component of two ECM-mix complexes. Individually, ECM proteins had both common and unique properties on the growth and differentiation of UCB CD34+ cells; some ECM proteins favoured the differentiation of some lineages over that of others (e.g. FN for erythroids), some the expansion of HPCs (e.g. LN and megakaryocyte (MK) progenitor) while others had less effects. Next, two ECM-mix complexes were tested; the first one contained all four ECM proteins (4ECMp), while the second 'basement membrane-like structure' was without COL I (3ECMp). Removal of COL I led to strong reductions in cell growth and HPCs expansion. Interestingly, the 4ECMp-mix complex reproducibly increased CD34+ (1.3-fold) and CD41+ (1.2-fold) cell expansions at day 6 (P < 0.05) versus control, and induced greater myeloid progenitor expansion (P < 0.05) than 3ECMp. In conclusion, these results suggest that optimization of BM ECM protein complexes could provide a better environment for the ex vivo expansion of haematopoietic progenitors than individual ECM protein.

Irradiated Mesenchymal Stem Cells improve the ex vivo expansion of Hematopoietic Progenitors by partly mimicking the bone marrow endosteal environment.

Mesenchymal Stem Cells (MSCs) regulate the growth and differentiation of Hematopoietic Progenitor cells (HPCs) through the release of soluble factors or through their differentiation into osteoblasts. We recently demonstrated that expansion of megakaryocyte (MK) progenitors ex vivo had reached a plateau when CD34(+) cells were grown with two optimized cytokine cocktails developed for the growth of MK. Hence, we sought to determine whether co-culture of CD34(+) cells with Bone Marrow (BM) MSCs could further increase the expansion of myeloid and MK progenitors. First, we tested the impact of cell-cell contact and pre-irradiation treatment of the MSCs to identify the condition that best supports HPC expansion. This screen revealed that HPC expansions were generally greater in the non-contact conditions, and that pre-irradiation of the MSCs appeared to be of added benefits. Improved expansion of both myeloid and MK progenitors in co-culture with irradiated MSCs without contact was subsequently confirmed. Next, cytokine array profiling was carried out to investigate why irradiation promoted progenitor expansion. This revealed that the levels of as many as 33 factors were potentially altered. ELISA confirmed the significant up regulation of NT-3 and IGFBP-2. Since, these factors are known to be released by and important for osteogenic and endothelial cells, we investigated and confirmed that irradiation of MSCs induced their rapid differentiation into osteogenic-like cells, but not into endothelial-like cells. Supporting this finding, expansions of myeloid and MK progenitors were increased when CD34(+) cells were co-culture with MSCs-derived osteoblasts. Altogether, these results indicate that the improved expansion of HPCs obtained with irradiated MSCs is due in part to their differentiation into osteoblast-like cells, thereby recreating an endosteal-like environment that provides improved support for HPCs expansion.

Proteome analysis of rat bone marrow mesenchymal stem cell differentiation.

Bone marrow multipotent stromal cells (or mesenchymal stem cells; MSCs) have the capacity for renewal and the potential to differentiate in culture into several cell types including osteoblasts, chondrocytes, adipocytes, cardiomyocytes, and neurons. This study was designed to investigate the protein expression profiles of rat bone marrow MSCs during differentiation into adipogenic (by dexamethasone, isobutylmethylxanthine, insulin, and indomethacin), cardiomyogenic (by 5-azacytidine), chondrogenic (by ascorbic acid, insulin-transferrin-selenous acid, and transforming growth factor-ß1), and osteogenic (by dexamethasone, ß-glycerophosphate, and ascorbic acid) lineages by well-known differentiation inducers. Proteins extracted from differentiated MSCs were separated using two-dimensional gel electrophoresis (2-DE) and protein spots were detected using Sypro Ruby dye. Protein spots that were determined to be up- or down-regulated when the expression of corresponding spots (between weeks 1 and 2, 1 and 3, 1 and 4) showed an increase (≥2-fold) or decrease (≤0.5-fold) were successfully identified by MALDI-TOF-MS. In summary, 23 new proteins were identified either up- or down-regulated during differentiation experiments.

Proteome analysis of rat bone marrow mesenchymal stem cell subcultures.

Bone marrow mesenchymal stem cells (BM-MSCs) have the capacity for renewal and the potential to differentiate in culture into several cell types including osteoblasts, chondrocytes, adipocytes, astrocytes, myocytes, oligodendrocytes, and neurons. Albeit previous reports demonstrated some of the effects of extensive subculturing on MSCs, the results still remain controversial. The aim of this study was to generate proteome maps of undifferentiated rat BM-MSCs, and identify differentially regulated proteins during serial subcultures within the first 10 passages. Proteins extracted from Wistar rat BM-MSCs were separated by two-dimensional gel electrophoresis and about 1000 protein spots were detected using the Sypro Ruby dye. Among them, 106 selected spots were digested with trypsin for mass spectrometry analysis, and 31 proteins were successfully identified by MALDI-TOF-MS. Here, 18 differentially expressed proteins are reported for the first time; these proteins are classified into 8 functional categories: metabolism, signal transduction, cell adhesion and growth, cytoskeleton, cell cycle, protein degradation, cell-cell interaction, and ion transfer. These proteins are reported to be involved in cell proliferation and differentiation through different signaling pathways. These studies suggest that differentially regulated passage-specific proteins may play a role in the decrease of proliferation potential under serial subculturing. The molecular mechanisms of rat BM-MSCs are discussed at the proteome level.