•Evaluation of mitochondrial function in PBMC at different time points.•Sex differences in mitochondrial function and serum melatonin concentrations.•Mitochondrial parameters and melatonin blood ...levels were lower in males.•Endogenous melatonin concentration may influence mitochondrial function.•Studies on mitochondrial function should consider endogenous melatonin levels.
Melatonin blood levels vary depending on the circadian rhythm. It also stimulates antioxidant enzymes and has positive effects on mitochondrial function. The current study investigated the effects of endogenously released melatonin on adenosine triphosphate (ATP) levels and mitochondrial respiration in peripheral blood mononuclear cells (PBMC).
The current study included 20 healthy adults (mean age 25,7 ± 3.4 years). Blood was collected at 8 a.m. and 2 p.m. The activity of mitochondrial respiratory complexes and ATP levels were determined in isolated PBMC. Melatonin concentrations were determined in serum samples. Sleep behavior was assessed.
In PBMCs isolated from blood samples of males, respiration of mitochondrial complex IV and ATP levels as well as serum melatonin concentration were significantly lower at 2 a.m. compared to the samples collected at 8 p.m. Mitochondrial parameters and melatonin blood levels were equal at both time points in the samples isolated from females.
Although our results show that the amount of melatonin secreted may have had an influence, further investigation is needed to determine the importance of melatonin and other factors in measuring the mitochondrial function of PBMC.
Abstract
Background
The expression of the endonuclease Dicer in macrophages decreases atherosclerosis and necrotic core formation by producing microRNAs such as miR-10a. This effect of Dicer is ...associated with enhanced mitochondrial respiration in lipid-loaded macrophages. However, the mechanism by which Dicer-dependent production of miRNAs in lipid-loaded macrophages regulates mitochondrial function is unclear.
Purpose
We aimed to determine the effect of Dicer on lipid-loaded macrophages in the context of atherosclerosis.
Methods
Mice with a myeloid cell-specific knockout of Dicer (Lys-Cre/Dicerflox/flox/Apoe−/− mice M-Dicer−/−) and control mice (Lys-Cre/DicerWT/WT/Apoe−/− mice M-Dicer+/+) were fed a high-fat diet (HFD) for 24 weeks. The oxygen consumption rate (OCR) in aortic arch plaques was studied ex vivo by Seahorse Flux XF 24 Analyzer. Bone marrow-derived macrophages (BMDMs) were stimulated with oxLDL (100 μg/mL) for 72 h. Lipid-loaded macrophages were used for proteomic analysis by mass spectrometry. RIP-prime- seq was performed in tAgo2 immunoprecipitates (IP) from Dicer+/+ and Dicer−/− BMDMs. The miRNA expression profile was determined in lipid-loaded BMDMs by NanoString technology. Stat1 phosphorylation was determined in lipid-loaded macrophages by Jess automated western blot system (ProteinSimple).
Result
The OCR in aortic arch tissue with plaques was higher than in those without plaques in M-Dicer+/+ mice after 24 weeks of HFD feeding. Dicer knockout in macrophages decreased the OCR in aortic arch tissues with plaques but not in aortic arch tissues without plaques (n=3–4, p<0.05). The proteomic analysis of oxLDL-treated BMDMs indicated that Dicer knockout activated the type I interferon signaling pathway by up-regulating the expression of STAT1/2 and interferon-stimulated genes, such as ISG15. Proteins related to mitochondrial DNA were upregulated (e.g., Dnmt3a) or downregulated (e.g., Tfam) by Dicer knockout (n=5, adj.p<0.05). RIP-prime-seq from BMDMs showed that 1376 transcripts were significantly enriched in the tAgo IP from Dicer+/+ compared with that from Dicer−/− BMDMs (n=3–5, adj.p<0.05) including Dnmt3a and Stat2. STAT1 phosphorylation was increased in Dicer−/− compared with Dicer+/+ BMDMs. Among the 299 miRNAs downregulated by Dicer knockout in lipid-loaded macrophages (n=6, adj.p<0.05), miR-29 and miR-30 have highly conserved binding sites (predicted by TargetScan) for Dnmt3a.
Conclusion
Our results indicate that Dicer expression in lipid-loaded macrophages limits Stat1/2-driven type I interferon response due to mitochondrial damage. This effect may be mediated by the suppression of Dnmt3a by miRNAs such as miR-29 and miR-30. This suggests that targeting Dnmt3a-mediated mitochondrial damage in lipid-loaded macrophages by miRNAs may be therapeutic strategy to limit atherosclerosis.
Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): DFG
The electric vehicles (EVs) are being developed at a rapid pace today and offer considerable environmental and economic benefits, as well as the ability to respond to demand (DR). The EV load ...scheduling provides end energy users with a method of reducing their electricity bills as well as reducing the peak load demand burden on utilities. This work seeks to identify the ideal power flow and lower the total daily charging costs of PHEVs based on various restrictions, such as power balancing constraints and battery charging/discharging limits. In the present study, a mathematical model of electric vehicles is used as a way to represent loads and energy sources during charging and discharging. When power costs are low or demand is low, the charging approach is utilized. When prices are high and demand is high, the energy that has been saved is used. The mathematical findings employing JAYA optimization techniques for load balancing and cost reduction support the advantages of the suggested energy management approach. The suggested approach outperforms standard approaches in a number of key ways.
The present study attempts to decipher the seasonal variations in hydro-geochemistry of groundwater in the Terekhol River Basin, western coastal region, Maharashtra, India. A total of 65 groundwater ...samples of post-monsoon (POMS) and pre-monsoon (PRMS) seasons were collected and analyzed for major ion composition using standard analytical procedures of APHA. Piper and Gibbs plots is used to elucidate the controlling factors which altering the groundwater composition. Scatter plots of ions indicate that major ions from lithologies exposed in the study area and anthropogenic activities are altering the groundwater chemistry. Statistical analysis includes correlation, factor analysis and cluster analysis used to interpret the hydrochemical data. As compared to the WHO drinking standards, all the groundwater samples are fit for drinking. Irrigation water suitability was ascertained based on SAR, %Na and KR indices. Overall, the groundwater chemistry in study area is reflects changes in natural processes rather than anthropogenic inputs.
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•Appraisal of groundwater for drinking and irrigation uses in the western coastal part of Maharashtra•Hydrogeochemical characteristics of groundwater from the Terekhol river basin•Influence of geogenic and anthropogenic inputs on groundwater quality•Spatial variations of ions in the study area•The study is integrated with hydrogeochemical, geospatial and statistical approaches.
The behavioral features of neuropathic pain are not sexually dimorphic despite sex differences in the underlying neuroimmune signaling. This raises questions about whether neural processing is ...comparably altered. Here, we test whether the K+-Cl− co-transporter KCC2, which regulates synaptic inhibition, plays an equally important role in development of neuropathic pain in male and female rodents. Past studies on KCC2 tested only males. We find that inhibiting KCC2 in uninjured animals reproduces behavioral and electrophysiological features of neuropathic pain in both sexes and, consistent with equivalent injury-induced downregulation of KCC2, that counteracting chloride dysregulation reverses injury-induced behavioral and electrophysiological changes in both sexes. These findings demonstrate that KCC2 downregulation contributes equally to pain hypersensitivity in males and females. Whereas diverse (and sexually dimorphic) mechanisms regulate KCC2, regulation of intracellular chloride relies almost exclusively on KCC2. Directly targeting KCC2 thus remains a promising strategy for treatment of neuropathic pain in both sexes.
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•Different neuroimmune signaling pathways cause neuropathic pain in males and females•Downregulation of KCC2 is equally important for pain pathogenesis in each sex•KCC2 is regulated in many ways but is uniquely responsible for regulating chloride•KCC2 is a conceptually better therapeutic target than sex-specific mechanisms
Neuropathic pain arises in males and females through distinct neuroimmune signaling. Yet the behavioral (or clinical) features of neuropathic pain are not sexually dimorphic. Mapplebeck et al. demonstrate that KCC2—though regulated in multiple, sex-specific ways—is uniquely responsible for the synaptic disinhibition causing neuropathic pain in both sexes.
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•Ex-situ microwave reactor was used to heat catalyst bed for pyrolysis upgrading.•Results were compared with conventional catalytic reactor.•Microwave heating yielded higher aromatic ...compounds.•Catalyst deactivation due to coking was lower in microwave reactor.•30% decrease in energy input for microwave reactor.
Microwave heating offers a number of advantages over conventional heating methods, such as, rapid and volumetric heating, precise temperature control, energy efficiency and lower temperature gradient. In this article we demonstrate the use of 2450MHz microwave traveling wave reactor to heat the catalyst bed for thermo-catalytic upgrading of pyrolysis vapors. HZSM-5 catalyst was tested at three different temperatures (290°, 330° and 370°C) at a catalyst to biomass ratio of 2. Results were compared with conventional heating and induction heating method of catalyst bed. The yields of aromatic compounds and coke deposition were dependent on temperature and method of heating. Microwave heating yielded higher aromatic compounds and lower coke deposition. Microwave heating was also energy efficient compared to conventional reactors. The rate of catalyst deterioration was lower for catalyst heated in microwave system.
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