Tunable Supramolecular Hydrogels for Selection of Lineage-Guiding Metabolites in Stem Cell Cultures

Stem cells are known to differentiate in response to the chemical and mechanical properties of the substrates on which they are cultured. Thus, supramolecular biomaterials with tunable properties are well suited for the study of stem cell differentiation. In this report, we exploited this phenomenon by combining stem cell differentiation in hydrogels with variable stiffness and metabolomics analysis to identify specific bioactive lipids that are uniquely used up during differentiation. To achieve this, we cultured perivascular stem cells on supramolecular peptide gels of different stiffness, and metabolite depletion followed. On soft (1 kPa), stiff (13 kPa), and rigid (32 kPa) gels, we observed neuronal, chondrogenic, and osteogenic differentiation, respectively, showing that these stem cells undergo stiffness-directed fate selection. By analyzing concentration variances of >600 metabolites during differentiation on the stiff and rigid gels (and focusing on chondrogenesis and osteogenesis as regenerative targets, respectively), we identified that specific lipids (lysophosphatidic acid and cholesterol sulfate, respectively), were significantly depleted. We propose that these metabolites are therefore involved in the differentiation process. In order to unequivocally demonstrate that the lipid metabolites that we identified play key roles in driving differentiation, we subsequently demonstrated that these individual lipids can, when fed to standard stem cell cultures, induce differentiation toward chondrocyte and osteoblast phenotypes. Our concept exploits the design of supramolecular biomaterials as a strategy for discovering cell-directing bioactive metabolites of therapeutic relevance

Effects of arm swing exercise training on cardiac autonomic modulation, cardiovascular risk factors, and electrolytes in persons aged 60–80 years with prehypertension: A randomized controlled trial

Background/Objective: This study aimed to investigate the effect and carry-over effect of arm swing exercise (ASE) training on cardiac autonomic modulation, cardiovascular risk factors, and blood electrolytes in older persons with prehypertension. Methods: Subjects were 50 individuals with prehypertension (aged 66.90 ± 5.50 yr, body mass index 23.84 ± 3.65 kg/m2). They were randomly assigned into ASE group and control group. Subjects in the ASE group underwent an ASE training program for 3 months at a frequency of 30 min/day, 3 days/week. Subjects in the control group maintained their daily routine activities minus regular exercise. Blood pressure, heart rate variability (HRV), cardiovascular risk factors including blood glucose, lipid profile, high-sensitive C-reactive protein (hsCRP), and electrolytes were evaluated on 3 occasions: before and after the 3-month intervention, and 1 month after intervention ended. Results: Following the 3-month intervention, systolic blood pressure (SBP) and serum hsCRP concentration were significantly lower, while serum high-density lipoprotein (HDL)-cholesterol, potassium (K+), magnesium (Mg2+) concentrations, standard deviation of normal R-R intervals (RMSSD) and high frequency (HF) power values were higher in the ASE group when compared with the control group (p < 0.05). At the 1-month follow-up interval, SBP and serum hsCRP concentration remained lower while serum HDL-cholesterol and K+ concentrations remained higher in the ASE group as compared to the control group (p < 0.05). Conclusion: ASE training decreased SBP and serum hsCRP concentration, increased serum HDL-cholesterol, K+, and Mg2+ concentrations and increased RMSSD and HF power values in older persons with prehypertension. In addition, there were carry-over effects of ASE training i.e. decreased SBP and serum hsCRP concentration as well as increased serum HDL-cholesterol and K+ concentrations. Keywords: Blood pressure, Exercise, Cardiovascular disease, Heart rate variability, Electrolyt

Anticancer and anti-angiogenic activities of mannooligosaccharides extracted from coconut meal on colorectal carcinoma cells in vitro

Colorectal carcinoma (CRC) is one of the most common malignancies, though there are no effective therapeutic regimens at present. This study aimed to investigate the inhibitory effects of mannooligosaccharides extracted from coconut meal (CMOSs) on the proliferation and migration of human colorectal cancer HCT116 cells in vitro. The results showed that CMOSs exhibited significant inhibitory activity against HCT116 cell proliferation in a concentration-dependent manner with less cytotoxic effects on the Vero normal cells. CMOSs displayed the ability to increase the activation of caspase-8, –9, and –3/7, as well as the generation of reactive oxygen species (ROS). Moreover, CMOSs suppressed HCT116 cell migration in vitro. Interestingly, treatment of human microvascular endothelial cells (HMVECs) with CMOSs resulted in the inhibition of cell proliferation, cell migration, and capillary-like tube formation, suggesting its anti-vascular angiogenesis. In summary, the results of this study indicate that CMOSs could be a valuable therapeutic candidate for CRC treatment