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Human Milk Oligosaccharides Mediate the Crosstalk Between Intestinal Epithelial Caco-2 Cells and Lactobacillus Plantarum WCFS1 in an In Vitro Model with Intestinal Peristaltic Shear Force

Background: The intestinal epithelial cells, food molecules, and gut microbiota are continuously exposed to intestinal peristaltic shear force. Shear force may impact the crosstalk of human milk oligosaccharides (hMOs) with commensal bacteria and intestinal epithelial cells. Objectives: We investigated how hMOs combined with intestinal peristaltic shear force impact intestinal epithelial cells and crosstalk with a commensal bacterium. Methods: We applied the Ibidi system to mimic intestinal peristaltic shear force. Caco-2 cells were exposed to a shear force (5 dynes/cm2) for 3 d, and then stimulated with the hMOs, 2'-fucosyllactose (2'-FL), 3-FL, and lacto-N-triose II (LNT2). In separate experiments, Lactobacillus plantarum WCFS1 adhesion to Caco-2 cells was studied with the same hMOs and shear force. Effects were tested on gene expression of glycocalyx-related molecules (glypican 1 [GPC1], hyaluronan synthase 1 [HAS1], HAS2, HAS3, exostosin glycosyltransferase 1 [EXT1], EXT2), defensin β-1 (DEFB1), and tight junction (tight junction protein 1 [TJP1], claudin 3 [CLDN3]) in Caco-2 cells. Protein expression of tight junctions was also quantified. Results: Shear force dramatically decreased gene expression of the main enzymes for making glycosaminoglycan side chains (HAS3 by 43.3% and EXT1 by 68.7%) (P <0.01), but did not affect GPC1 which is the gene responsible for the synthesis of glypican 1 which is a major protein backbone of glycocalyx. Expression of DEFB1, TJP1, and CLDN3 genes was decreased 60.0-94.9% by shear force (P <0.001). The presence of L. plantarum WCFS1 increased GPC1, HAS2, HAS3, and ZO-1 expression by 1.78- to 3.34-fold (P <0.05). Under shear force, all hMOs significantly stimulated DEFB1 and ZO-1, whereas only 3-FL and LNT2 enhanced L. plantarum WCFS1 adhesion by 1.85- to 1.90-fold (P <0.01). Conclusions: 3-FL and LNT2 support the crosstalk between the commensal bacterium L. plantarum WCFS1 and Caco-2 intestinal epithelial cells, and shear force can increase the modulating effects of hMOs

Коррекция состояния иммунной системы крыс с адъювантным артритом введением липидной фракции плаценты

Введення ліпідної фракції плаценти, отриманої методом кріогенного молекулярного фракціонування, на фоні розвитку ад’ювантного артриту оказує корегуючий вплив у відношенні як вмісту, так і функціональної активності регуляторних Т-клітин регіональних лімфовузлів, що призводить до зниження інтенсивності клінічних ознак захворювання.Injection of placental lipid fraction obtained by cryogenic molecular fractionation method on the background of adjuvant arthritis development has a correcting influence in relation to both content and functional activity of regulatory T-cells of regional lymph nodes which leads to a decrease in intensity of clinical signs of the disease

Effectiveness of attentional bias modification training as add-on to regular treatment in alcohol and cannabis use disorder:A multicenter randomized control trial

BACKGROUND: Attentional bias for substance-relevant cues has been found to contribute to the persistence of addiction. Attentional bias modification (ABM) interventions might, therefore, increase positive treatment outcome and reduce relapse rates. The current study investigated the effectiveness of a newly developed home-delivered, multi-session, internet-based ABM intervention, the Bouncing Image Training Task (BITT), as an add-on to treatment as usual (TAU). METHODS: Participants (N = 169), diagnosed with alcohol or cannabis use disorder, were randomly assigned to one of two conditions: the experimental ABM group (50%; TAU+ABM); or the control group (50%; split in two subgroups the TAU+placebo group and TAU-only group, 25% each). Participants completed baseline, post-test, and 6 and 12 months follow-up measures of substance use and craving allowing to assess long-term treatment success and relapse rates. In addition, attentional bias (both engagement and disengagement), as well as secondary physical and psychological complaints (depression, anxiety, and stress) were assessed. RESULTS: No significant differences were found between conditions with regard to substance use, craving, relapse rates, attentional bias, or physical and psychological complaints. CONCLUSIONS: The findings may reflect unsuccessful modification of attentional bias, the BITT not targeting the relevant process (engagement vs. disengagement bias), or may relate to the diverse treatment goals of the current sample (i.e., moderation or abstinence). The current findings provide no support for the efficacy of this ABM approach as an add-on to TAU in alcohol or cannabis use disorder. Future studies need to delineate the role of engagement and disengagement bias in the persistence of addiction, and the role of treatment goal in the effectiveness of ABM interventions

Expression of a retinoic acid signature in circulating CD34 cells from coronary artery disease patients

<p>Abstract</p> <p>Background</p> <p>Circulating CD34+ progenitor cells have the potential to differentiate into a variety of cells, including endothelial cells. Knowledge is still scarce about the transcriptional programs used by CD34+ cells from peripheral blood, and how these are affected in coronary artery disease (CAD) patients.</p> <p>Results</p> <p>We performed a whole genome transcriptome analysis of CD34+ cells, CD4+ T cells, CD14+ monocytes, and macrophages from 12 patients with CAD and 11 matched controls. CD34+ cells, compared to other mononuclear cells from the same individuals, showed high levels of KRAB box transcription factors, known to be involved in gene silencing. This correlated with high expression levels in CD34+ cells for the progenitor markers HOXA5 and HOXA9, which are known to control expression of KRAB factor genes. The comparison of expression profiles of CD34+ cells from CAD patients and controls revealed a less naïve phenotype in patients' CD34+ cells, with increased expression of genes from the Mitogen Activated Kinase network and a lowered expression of a panel of histone genes, reaching levels comparable to that in more differentiated circulating cells. Furthermore, we observed a reduced expression of several genes involved in CXCR4-signaling and migration to SDF1/CXCL12.</p> <p>Conclusions</p> <p>The altered gene expression profile of CD34+ cells in CAD patients was related to activation/differentiation by a retinoic acid-induced differentiation program. These results suggest that circulating CD34+ cells in CAD patients are programmed by retinoic acid, leading to a reduced capacity to migrate to ischemic tissues.</p

The impact of emotional well-being on long-term recovery and survival in physical illness: a meta-analysis

This meta-analysis synthesized studies on emotional well-being as predictor of the prognosis of physical illness, while in addition evaluating the impact of putative moderators, namely constructs of well-being, health-related outcome, year of publication, follow-up time and methodological quality of the included studies. The search in reference lists and electronic databases (Medline and PsycInfo) identified 17 eligible studies examining the impact of general well-being, positive affect and life satisfaction on recovery and survival in physically ill patients. Meta-analytically combining these studies revealed a Likelihood Ratio of 1.14, indicating a small but significant effect. Higher levels of emotional well-being are beneficial for recovery and survival in physically ill patients. The findings show that emotional well-being predicts long-term prognosis of physical illness. This suggests that enhancement of emotional well-being may improve the prognosis of physical illness, which should be investigated by future research

The effect of chronic kidney disease on tissue formation of in situ tissue-engineered vascular grafts

Vascular in situ tissue engineering encompasses a single-step approach with a wide adaptive potential and true off-the-shelf availability for vascular grafts. However, a synchronized balance between breakdown of the scaffold material and neo-tissue formation is essential. Chronic kidney disease (CKD) may influence this balance, lowering the usability of these grafts for vascular access in end-stage CKD patients on dialysis. We aimed to investigate the effects of CKD on in vivo scaffold breakdown and tissue formation in grafts made of electrospun, modular, supramolecular polycarbonate with ureido-pyrimidinone moieties (PC-UPy). We implanted PC-UPy aortic interposition grafts (n = 40) in a rat 5/6th nephrectomy model that mimics systemic conditions in human CKD patients. We studied patency, mechanical stability, extracellular matrix (ECM) components, total cellularity, vascular tissue formation, and vascular calcification in CKD and healthy rats at 2, 4, 8, and 12 weeks post-implantation. Our study shows successful in vivo application of a slow-degrading small-diameter vascular graft that supports adequate in situ vascular tissue formation. Despite systemic inflammation associated with CKD, no influence of CKD on patency (Sham: 95% vs CKD: 100%), mechanical stability, ECM formation (Sirius red +, Sham 16.5% vs CKD 25.0%-p:0.83), tissue composition, and immune cell infiltration was found. We did find a limited increase in vascular calcification at 12 weeks (Sham 0.08% vs CKD 0.80%-p:0.02) in grafts implanted in CKD animals. However, this was not associated with increased stiffness in the explants. Our findings suggest that disease-specific graft design may not be necessary for use in CKD patients on dialysis. </p

Examination and measurement of coping among adolescents with spinal cord injury

Objectives: To describe coping strategy use in adolescents with spinal cord injury (SCI), to explore the underlying factor structure of a measure of coping among adolescents with SCI and to assess relationships between coping and psychosocial outcomes. Setting: Multiple pediatric SCI centers in the United States. Methods: One hundred and eighty-two participants aged 13–17 years who experienced an SCI completed measures including the Kidcope, Children’s Depression Inventory, Revised Children’s Manifest Anxiety Scale and the Pediatric Quality of Life Inventory. Results: Participants reported that cognitive restructuring and resignation are the most used coping strategies, whereas social support, emotional regulation (calming) and cognitive restructuring are the most effective coping strategies. An exploratory factor analysis revealed that a three-factor solution provided the most parsimonious model for the relationships between the different coping strategies. However, only one of the three factors had acceptable internal consistency. This factor comprised escape-oriented coping strategies or an avoidant approach to coping with the sequelae of SCI. After controlling for demographic/injury-related factors, higher scores on the escape-oriented factor were associated with the lower quality of life and higher levels of depression and anxiety symptomatology. Conclusion: Escape-oriented coping is associated with maladaptive psychosocial outcomes in adolescents with SCI. These adolescents report that active coping strategies are most effective in reducing SCI-related distress. Coping strategy use may mediate psychosocial outcomes in adolescents with SCI and represent an intervention target in adolescents who overly rely on escape-oriented coping