Djulis Hull Enhances the Efficacy of Ferric Citrate Supplementation via Restoring Normal Iron Efflux through the IL-6-Hepcidin-Ferroportin Pathway in High-Fat-Diet-Induced Obese Rats.

Obesity-related functional iron disorder remains a major nutritional challenge. We evaluated the effects of djulis hull (DH) on iron metabolism in 50% high-fat-diet-induced obese rats supplemented with ferric citrate (2 g iron/kg diet) for 12 weeks. DH supplementation (5, 10, 15% dry weight/kg diet) significantly increased serum and hepatic iron but decreased appetite hormones, body weight, hepcidin, and liver inflammation (all p < 0.05). The Spearman correlation showed that appetite hormones were negatively associated with iron but positively correlated with liver hepcidin (all p < 0.05). A Western blot analysis showed that DH significantly downregulated hepatic hepcidin through the IL-6-JAK-STAT3 and enhanced ferroportin (Fpn) via the Keap1-Nrf2 and PHD2-HIF-2α. An in vitro study revealed that major bioactive compounds of DH, hexacosanol, and squalene suppressed LPS-induced IL-6 and hepcidin but enhanced Fpn expression in activated THP-1 cells. In conclusion, DH may exert nutraceutical properties for the treatment of functional iron disorder and restoration of iron efflux may have beneficial effects on weight control.

Melatonin enhances osteogenic differentiation of dental pulp mesenchymal stem cells by regulating MAPK pathways and promotes the efficiency of bone regeneration in calvarial bone defects.

BACKGROUND: Mesenchymal stem cell (MSC)-based tissue engineering plays a major role in regenerative medicine. However, the efficiency of MSC transplantation and survival of engrafted stem cells remain challenging. Melatonin can regulate MSC biology. However, its function in the osteogenic differentiation of dental pulp-derived MSCs (DPSCs) remains unclear. We investigated the effects and mechanisms of melatonin on the osteogenic differentiation and bone regeneration capacities of DPSCs. METHODS: The biological effects and signaling mechanisms of melatonin with different concentrations on DPSCs were evaluated using a proliferation assay, the quantitative alkaline phosphatase (ALP) activity, Alizarin red staining, a real-time polymerase chain reaction, and a western blot in vitro cell culture model. The in vivo bone regeneration capacities were assessed among empty control, MBCP, MBCP + DPSCs, and MBCP + DPSCs + melatonin preconditioning in four-created calvarial bone defects by using micro-computed tomographic, histological, histomorphometric, and immunohistochemical analyses after 4 and 8 weeks of healing. RESULTS: In vitro experiments revealed that melatonin (1, 10, and 100 µM) significantly and concentration-dependently promoted proliferation, surface marker expression (CD 146), ALP activity and extracellular calcium deposition, and osteogenic gene expression of DPSCs (p < 0.05). Melatonin activated the protein expression of ALP, OCN, and RUNX-2 and inhibited COX-2/NF-κB expression. Furthermore, the phosphorylation of mitogen-activated protein kinase (MAPK) p38/ERK signaling was significantly increased in DPSCs treated with 100 µM melatonin, and their inhibitors significantly decreased osteogenic differentiation. In vivo experiments demonstrated that bone defects implanted with MBCP bone-grafting materials and melatonin-preconditioned DPSCs exhibited significantly greater bone volume fraction, trabecular bone structural modeling, new bone formation, and osteogenesis-related protein expression than the other three groups at 4 and 8 weeks postoperatively (p < 0.05). CONCLUSIONS: These results suggest that melatonin promotes the proliferation and osteogenic differentiation of DPSCs by regulating COX-2/NF-κB and p38/ERK MAPK signaling pathways. Preconditioning DPSCs with melatonin before transplantation can efficiently enhance MSCs function and regenerative capacities.

Soluble CD163-Associated Dietary Patterns and the Risk of Metabolic Syndrome.

Elevated soluble cluster of differentiation 163 (sCD163) concentrations, a marker of macrophage activation, are associated with obesity. Weight reduction decreases circulating CD163 levels, and changes in sCD163 levels are associated with improved metabolic dysfunction. Currently, the relationship between sCD163 and diet remains unclear. This study investigated dietary patterns associated with sCD163 concentrations and its predictive effect on metabolic syndrome (MetS). Data on anthropometrics, blood biochemistry, and a food frequency questionnaire were collected from 166 Taiwanese adults. sCD163 levels independently predicted MetS (odds ratio (OR): 5.35; 95% confidence interval (CI): 2.13~13.44, p < 0.001), non-alcoholic fatty liver disease (OR: 2.19; 95% CI: 1.03~4.64, p < 0.001), and central obesity (OR: 3.90; 95% CI: 1.78~8.55, p < 0.001), after adjusting for age and sex. An adjusted linear regression analysis revealed strong correlations between levels of sCD163 and aspartate transaminase (AST) (ß = 0.250 (0.023~0.477), p < 0.05) and red blood cell aggregation (ß = 0.332 (0.035~0.628), p < 0.05). sCD163-associated dietary pattern scores (high frequencies of consuming noodles and desserts, and eating at home, and a low intake frequency of steamed/boiled/raw food, white/light-green-colored vegetables, orange/red/purple-colored vegetables, dairy products, seafood, dark-green leafy vegetables, and soy products) were positively correlated with MetS, liver injury biomarkers, and sCD163 levels (all p for trend < 0.05). Individuals with the highest dietary pattern scores (tertile 3) had a 2.37-fold [OR: 2.37; 95% CI: 1.04~5.37, p < 0.05] higher risk of MetS compared to those with the lowest scores (tertile 1). Overall, the study findings suggest the importance of a healthy dietary pattern in preventing elevated sCD163 levels and diet-related chronic disease such as MetS.