METHODS: HepG2 cells were treated with different concentrations of KMF and 0.5 mM palmitate (PA) for 24 h. The mRNA and protein levels of genes involved in lipid metabolism were evaluated using real-time PCR and western blot. The expression of Nrf2 was silenced using siRNA.
RESULTS: Data indicated that KMF (20 μM) reversed PA-induced increased triglyceride (TG) levels and total lipid content. These effects were accompanied by down-regulation of the mRNA and protein levels of lipogenic genes (FAS, ACC and SREBP1), and up-regulation of genes related to fatty acid oxidation (CPT-1, HADHα and PPARα). Kaempferol significantly decreased the levels of the oxidative stress markers (ROS and MDA) and enhanced the activities of antioxidant enzymes SOD and GPx in PA-challenged cells. Luciferase analysis showed that KMF increased the transactivation of Nrf2 in hepatocytes. The results also revealed that KMF-mediated activation of Nrf2 target genes was suppressed by Nrf2 siRNA. Furthermore, Nrf2 siRNA abolished the KMF-induced reduction in ROS and MDA levels in PA treated cells. In addition, the inhibitory effect of KMF on TG levels and the mRNA and protein levels of FAS, ACC and SREPB-1 were significantly abolished by Nrf2 inhibition. Nrf2 inhibition also suppressed the KMF-induced activation of genes involved in β oxidation (CPT-1 and PPAR-α).
CONCLUSION: The results suggest that KMF protects HepG2 cells from PA-induced lipid accumulation via activation of the Nrf2 signaling pathway.
METHODS: A two-level factorial design was employed to optimize the removal of chemical oxygen demand (COD) and turbidity using Aspergillus niger. Bioremediation of SS was performed through submerged fermentation (SmF) under several independent variables, including temperature (20-40 °C), agitation speed (100-200 RPM), fermentation duration (72-240 h), and initial sample concentration (20-100%). The characteristics of the treated SS were then compared to that of raw sludge.
RESULTS: Optimal COD and turbidity removal were achieved at 37 °C 100 RPM, 156 h, and 100% sludge. The analysis of variance (ANOVA) revealed a significant effect of selective individual and interacting variables (p oxygen demand (BOD), oil and grease (OG), color, and carbon content. In short, this study demonstrated the effectiveness of A. niger in treating SS through the application of a two-level factorial design.
OBJECTIVES: To determine whether nasal continuous positive airway pressure (NCPAP), applied immediately after extubation of preterm infants, reduces the incidence of extubation failure and the need for additional ventilatory support, without clinically important adverse events.
SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and trial registries on 22 September 2023 using a revised strategy. We searched conference abstracts and the reference lists of included studies and relevant systematic reviews.
SELECTION CRITERIA: Eligible trials employed random or quasi-random allocation of preterm infants undergoing extubation. Eligible comparisons were NCPAP (delivered by any device and interface) versus head box oxygen, extubation to room air, or any other form of low-pressure supplemental oxygen. We grouped the comparators under the term no continuous positive airway pressure (no CPAP).
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the risk of bias and extracted data from the included studies. Where studies were sufficiently similar, we performed a meta-analysis, calculating risk ratios (RRs) with their 95% confidence intervals (CIs) for dichotomous data. For the primary outcomes that showed an effect, we calculated the number needed to treat for an additional beneficial outcome (NNTB). We used the GRADE approach to assess the certainty of the evidence for clinically important outcomes.
MAIN RESULTS: We included nine trials (with 726 infants) in the quantitative synthesis of this updated review. Eight studies were conducted in high-income countries between 1982 and 2005. One study was conducted in Chile, which was classified as upper-middle income at the time of the study. All studies used head box oxygen in the control arm. Risk of bias was generally low. However, due to the inherent nature of the intervention, no studies incorporated blinding. Consequently, the neonatal intensive care unit staff were aware of the assigned group for each infant, and we judged all studies at high risk of performance bias. However, we assessed blinding of the outcome assessor (detection bias) as low risk for seven studies because they used objective criteria to define both primary outcomes. NCPAP compared with no CPAP may reduce the risk of extubation failure (RR 0.62, 95% CI 0.51 to 0.76; risk difference (RD) -0.17, 95% -0.23 to -0.10; NNTB 6, 95% CI 4 to 10; I2 = 55%; 9 studies, 726 infants; low-certainty evidence) and endotracheal reintubation (RR 0.79, 95% 0.64 to 0.98; RD -0.07, 95% CI -0.14 to -0.01; NNTB 15, 95% CI 8 to 100; I2 = 65%; 9 studies; 726 infants; very low-certainty evidence), though the evidence for endotracheal reintubation is very uncertain. NCPAP compared with no CPAP may have little or no effect on bronchopulmonary dysplasia, but the evidence is very uncertain (RR 0.89, 95% CI 0.47 to 1.68; RD -0.03, 95% CI -0.22 to 0.15; 1 study, 92 infants; very low-certainty evidence). No study reported neurodevelopmental outcomes.
AUTHORS' CONCLUSIONS: NCPAP may be more effective than no CPAP in preventing extubation failure in preterm infants if applied immediately after extubation from invasive mechanical ventilation. We are uncertain whether it can reduce the risk of reintubation or bronchopulmonary dysplasia. We have no information on long-term neurodevelopmental outcomes. Although there is only low-certainty evidence for the effectiveness of NCPAP immediately after extubation in preterm infants, we consider there is no need for further research on this intervention, which has become standard practice.
METHODS: ASCs were cultured on chitosan nano-deposited surfaces to form 3D spheres. Mitochondrial activity and ATP production were assessed using MitoTracker staining, Seahorse XF analysis, and ATP luminescence assays. Single-cell RNA sequencing, followed by Ingenuity Pathway Analysis (IPA), was conducted to uncover key regulatory pathways, which were validated through molecular techniques. Pathway involvement was confirmed using epigenetic inhibitors or PPARγ-modulating drugs. Mitochondrial structural integrity and delivery efficiency were evaluated after isolation.
RESULTS: Chitosan-induced ASC spheres exhibited unique compact mitochondrial morphology, characterized by condensed cristae, enhanced mitochondrial activity, and increased ATP production through oxidative phosphorylation. High expressions of mitochondrial complex I genes and elevated levels of mitochondrial complex proteins were observed without an increase in reactive oxygen species (ROS). Epigenetic modification of H3K27me3 and PPARγ involvement were discovered and confirmed by inhibiting H3K27me3 with the specific EZH2 inhibitor GSK126 and by adding the PPARγ agonist Rosiglitazone (RSG). Isolated mitochondria from ASC spheres showed improved structural stability and delivery efficiency, suppressed the of inflammatory cytokines in LPS- and TNFα-induced inflamed cells, and rescued cells from damage, thereby enhancing function and promoting recovery.
CONCLUSION: Enhancing mitochondrial ATP production via the EZH2-H3K27me3-PPARγ pathway offers an alternative strategy to conventional cell-based therapies. High-functional mitochondria and delivery efficiency show significant potential for regenerative medicine applications.
Methods: This study was carried out at the Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia, between June 2016 and July 2017. Bone marrow cells were isolated from nine mice and cultured in a growth medium. Various concentrations of NAC between 0.125-2 μM were added to the culture for 48 hours; these cells were then compared to non-supplemented cells harvested from the remaining three mice as the control group. A trypan blue exclusion test was performed to determine cell viability, while intracellular ROS levels and genotoxicity were determined by hydroethidine staining and comet assay, respectively. The lineage commitment potential of erythroid, myeloid and pre-B-lymphoid progenitor cells was evaluated via colony-forming cell assay.
Results: NAC supplementation at 0.25, 0.5 and 2 μM significantly increased cell viability (P <0.050), while intracellular ROS levels significantly decreased at 0.25 and 0.5 μM (P <0.050). Moreover, DNA damage was significantly reduced at all NAC concentrations (P <0.050). Finally, the potential lineage commitment of the cells was not significantly affected by NAC supplementation (P >0.050).
Conclusion: The findings of this study indicate that NAC supplementation may potentially overcome the therapeutic limitations of ex vivo-maintained HSPCs.
METHODS: Semen specimens of 151 normozoospermic men were analyzed for ROS by chemiluminescence and classified according to seminal ROS levels [in relative light units (RLU)/s/106 sperm]: group 1 (n = 39): low (ROS