Melaleuca alternifolia concentrate (MAC) is the refined essential oil of the Australian native plant Melaleuca alternifolia. MAC has been reported to suppress the production of pro-inflammatory cytokines in both murine RAW264.7 macrophages and human monocytes stimulated with lipopolysaccharide (LPS). However, the mechanisms involved in this effect remain unclear. This study aims to delineate the molecular mechanisms that drive the anti-inflammatory activity of MAC and its active component, terpinen-4-ol, in macrophages. The effects of MAC on RAW264.7 cells were studied using western blotting, real-time PCR, an electrophoretic mobility shift assay (EMSA), and NF-$\kappa$B luciferase reporter assays. Our results showed that MAC significantly increased both the mRNA and protein levels of heme oxygenase-1 (HO-1) via p38 and JNK MAPK activation. In addition, we showed that MAC significantly increased the activation and nuclear translocation of NF-E2-related factor 2 (Nrf2), a key transcription factor regulating HO-1 induction. MAC was also associated with significant inhibition of iNOS expression, NO production, and NF-$\kappa$B activation. HO-1 was required for these anti-inflammatory effects as tin protoporphyrin IX (SnPPIX), an HO-1 inhibitor, abolished the effects of MAC on LPS-induced iNOS, NO, and NF-$\kappa$B activation. Our results indicate that MAC induces HO-1 expression in murine macrophages via the p38 MAPK and JNK pathways and that this induction is required for its anti-inflammatory activity.

Early initiation of enteral nutrition improves clinical outcomes in critical patients with serious burns. Post-pyloric tube feeding is a valuable therapeutic option for severely burned patients with poor gastric emptying. How early post-pyloric feeding can be initiated to provide more benefits to patients has not yet been examined. A fire erupted at a recreational water park in New Taipei City, Taiwan, on June 27, 2015. The results of early initiation versus delayed post-pyloric feeding in severely burned patients in this mass-casualty incident were compared. Door-to-post-pyloric feeding time ≤ 24 h was considered as early post-pyloric feeding (EPF) and that > 24 h was considered as delayed post-pyloric feeding (DPF). Thirteen patients with severe burn injuries (> 40% of the total body surface area) were assigned to undergo either EPF (five patients) or DPF (eight patients). This study is a “fortuitously controlled” study, and the authors were able to formulate and test whether EPF is better than DPF by comparing the two groups. In patients in the EPF, the intake of calories increased rapidly and was maintained throughout the study period. In addition, rapid restoration of plasma magnesium concentrations as well as pronounced recovery of platelet count in the EPF group was observed. In conclusion, our findings indicate that the time from injury to the onset of post-pyloric feeding is crucial, and EPF allows for the administration of calculated caloric needs. Therefore, EPF can be successfully initiated with beneficial outcomes of nutritional reconstruction in severely burned patients.

Background: Xanthelasma palpebrarum (XP) is a sign of hyperlipidemia and is closely linked to atherosclerosis. Since fatty liver shares similar risk factors with atherosclerosis, we hypothesized that patients with XP are also at risk of non-alcoholic fatty liver disease (NAFLD). Methods: In this retrospective cohort study, 37 patients with XP were compared with sex- and age-matched controls undergoing general health examination. Moreover, demographic information and lipid profiles were compared. The risk of NAFLD was evaluated using the hepatic steatosis and ZJU indices. In addition, we analyzed publicly available RNA sequencing data from the GSE48452 and GSE61260 datasets in the Gene Expression Omnibus database. Findings: Patients with XP had higher scores of hepatic steatosis index (37 ± 1.13 vs 32 ± 0.82, p=0.0006) and ZJU index (38.77 ± 1.0 vs 33.88 ± 0.74, p=0.0002). In addition, they had higher levels of lipid parameters, including total cholesterol, low-density lipoprotein (LDL), and fasting glucose. Among patients with fatty liver, individuals presenting with XP showed higher serum levels of total cholesterol (216 ± 10.4 vs 188.9 ± 7.6, p=0.04), fasting glucose (117.1 ± 6.4 vs 98.3 ± 2.4, p=0.002), and low-density lipoprotein (145.1 ± 8.7 vs 115.6 ± 6.4, p=0.009) than those without XP. In gene expression analysis, individuals presenting with non-alcoholic steatohepatitis showed higher Z scores of xanthelasma than those without non-alcoholic steatohepatitis. Conclusion: Our results suggest that individuals with XP have a higher risk of progression to NAFLD and develop a more severe dyslipidemia.

Background: Vitamin D contributes to bone health and extra-skeletal effects. The mechanisms underlying vitamin D metabolism have not been extensively evaluated. The relationships between vitamin D and inflammatory cytokines are debated. Our objective was to investigate whether supplemental interferons are associated with longitudinal change of vitamin D status in humans. Methods: A total of 48 patients with 24 or 48 weeks of pegylated interferon-α plus ribavirin therapy were examined for serum 25-hydroxyvitamin D (25[OH]D) level before treatment, at the end of treatment, and 24 weeks after treatment. In addition, we analyzed publicly available RNA sequencing data from accession GSE42697 and GSE7123 in the Gene Expression Omnibus. Findings: The overall sustained virologic response (SVR) rate was 62.5%. There was no statistically significant association between baseline 25(OH)D concentrations and liver fibrosis. In patients with SVR, serum 25(OH)D increased markedly at end-of-treatment and decreased markedly by the end of the 24-week follow-up period. In the non-SVR group, this treatment-dependent change was lost. In gene expression analysis, the vitamin D biosynthesis process was activated in subjects with SVR, but not in patients without SVR. Furthermore, vitamin D receptor (VDR) signaling in peripheral blood mononuclear cells (PBMCs) was triggered in marked responders but not in poor responders. Conclusion: In the aggregate, these data suggest that interferons have a regulatory influence on vitamin D status that can contribute to VDR signaling in PBMCs.