Spatial metabolomics reveal mechanisms of dexamethasone against pediatric pneumonia.

Currently, drugs are limited to treating pediatric pneumonia in clinical practice. It is urgent to find one new precise prevention and control therapy. The dynamically changing biomarkers during the development of pediatric pneumonia could help diagnose this disease, determine its severity, assess the risk of future events, and guide its treatment. Dexamethasone has been recognized as an effective agent with anti-inflammatory activity. However, its mechanisms against pediatric pneumonia remain unclear. In this study, spatial metabolomics was used to reveal the potential and characteristics of dexamethasone. Specifically, bioinformatics was first applied to find the critical biomarkers of differential expression in pediatric pneumonia. Subsequently, Desorption Electrospray Ionization mass spectrometry imaging-based metabolomics screened the differential metabolites affected by dexamethasone. Then, a gene-metabolite interaction network was built to mark functional correlation pathways for exploring integrated information and core biomarkers related to the pathogenesis and etiology of pediatric pneumonia. Further, these were validated by molecular biology and targeted metabolomics. As a result, genes of Cluster of Differentiation19, Fc fragment of IgG receptor IIb, Cluster of Differentiation 22, B-cell linker, Cluster of Differentiation 79B and metabolites of Triethanolamine, Lysophosphatidylcholine(18:1(9Z)), Phosphatidylcholine(16:0/16:0), phosphatidylethanolamine(O-18:1(1Z)/20:4(5Z,8Z,11Z,14Z)) were identified as the critical biomarkers in pediatric pneumonia. B cell receptor signaling pathway and glycerophospholipid metabolism were integrally analyzed as the main pathways of these biomarkers. The above data were illustrated using a Lipopolysaccharides-induced lung injury juvenile rat model. This work will provide evidence for the precise treatment of pediatric pneumonia.

Ecological thresholds of toxic plants for sheep production and ecosystem multifunctionality and their trade-off in an alpine meadow.

Toxic plants are a natural component of alpine meadow which co-evolved with Tibetan sheep for thousands of years. One challenge for indigenous herders is to know the ecological thresholds of toxic plants and maintain their vital functions in ways that are compatible with economic income and ecological conservation. To achieve this, field trials with Tibetan sheep grazing in alpine meadow were conducted to examine the ecological thresholds of toxic plants for sheep production and ecosystem functions and their trade-offs. Our results demonstrated that the changing point values of biomass proportion of toxic plants for dry matter intake and liveweight gain of sheep were 17% and 22%, respectively. The changing point value of biomass (richness) proportion of toxic plants for soil carbon accumulation index was 31% (59%), for soil nutrient cycling index was 38% (42%), and for ecosystem multifunctionality index was 28% (50%). The trade-off between liveweight gain of sheep and ecosystem multifunctionality first decreased and then increased along the gradient of biomass proportion of toxic plants (the value of changing point was 37%), and had a significant negative correlation with richness of toxic plants. In addition, structural equation modeling indicated that toxic plants can affect the trade-off between liveweight gain of sheep and ecosystem multifunctionality though increasing acid detergent fiber of plant and decreasing plant species richness, belowground biomass and soil total phosphorus. Consequently, opinions towards toxic plants should shift from the conventional view that they are serious threat to grassland ecosystem health to an inclusive understanding that they are beneficial to livestock and ecosystem functions under certain ecological thresholds.

Microencapsulation of Flaxseed Oil by Lentil Protein Isolate-κ-Carrageenan and -ι-Carrageenan Based Wall Materials through Spray and Freeze Drying.

Lentil protein isolate (LPI)-κ-carrageenan (κ-C) and -ι-carrageenan (ι-C) based microcapsules were prepared through spray-drying and freeze-drying to encapsulate flaxseed oil in order to reach final oil levels of 20% and 30%. Characteristics of the corresponding emulsions and their dried microcapsules were determined. For emulsion properties, all LPI-κ-C and LPI-ι-C emulsions remained 100% stable after 48 h, while the LPI emulsions destabilized quickly (p < 0.05) after homogenization mainly due to low emulsion viscosity. For spray-dried microcapsules, the highest yield was attributed to LPI-ι-C with 20% oil, followed by LPI-κ-C 20% and LPI-ι-C 30% (p < 0.05). Flaxseed oil was oxidized more significantly among the spray-dried capsules compared to untreated oil (p < 0.05) due to the effect of heat. Flaxseed oil was more stable in all the freeze-dried capsules and showed significantly lower oil oxidation than the untreated oil after 8 weeks of storage (p < 0.05). As for in vitro oil release profile, a higher amount of oil was released for LPI-κ-C powders under simulated gastric fluid (SGF), while more oil was released for LPI-ι-C powders under simulated gastric fluid and simulated intestinal fluid (SGF + SIF) regardless of drying method and oil content. This study enhanced the emulsion stability by applying carrageenan to LPI and showed the potential to make plant-based microcapsules to deliver omega-3 oils.

Ictal Source Locations and Cortico-Thalamic Connectivity in Childhood Absence Epilepsy: Associations with Treatment Response.

Childhood absence epilepsy (CAE), the most common pediatric epilepsy syndrome, is usually treated with valproic acid (VPA) and lamotrigine (LTG) in China. This study aimed to investigate the ictal source locations and functional connectivity (FC) networks between the cortices and thalamus that are related to treatment response. Magnetoencephalography (MEG) data from 25 patients with CAE were recorded at 300 Hz and analyzed in 1-30 Hz frequency bands. Neuromagnetic sources were volumetrically scanned with accumulated source imaging. The FC networks between the cortices and thalamus were evaluated at the source level through a connectivity analysis. Treatment outcome was assessed after 36-66 months following MEG recording. The children with CAE were divided into LTG responder, LTG non-responder, VPA responder and VPA non-responder groups. The ictal source locations and cortico-thalamic FC networks were compared to the treatment response. The ictal source locations in the post-dorsal medial frontal cortex (post-DMFC, including the medial primary motor cortex and the supplementary sensorimotor area) were observed in all LTG non-responders but in all LTG responders. At 1-7 Hz, patients with fronto-thalamo-parietal/occipital (F-T-P/O) networks were older than those with fronto-thalamic (F-T) networks or other cortico-thalamic networks (p = 0.000). The duration of seizures in patients with F-T-P/O networks at 1-7 Hz was longer than that in patients with F-T networks or other cortico-thalamic networks (p = 0.001). The ictal post-DMFC source localizations suggest that children with CAE might experience initial LTG monotherapy failure. Moreover, the cortico-thalamo-cortical network is associated with age. Finally, the cortico-thalamo-cortical network consists of anterior and posterior cortices and might contribute to the maintenance of discharges.

[In vivo transdermal penetration enhancing activity of essential oil from Zanthoxyli Pericarpium by using microdialysis technique].

The aim of this paper is to investigate the topical pharmacodynamics behavior of different lipophilic model drugs after treatment with essential oil from Zanthoxyli Pericarpium by using the cutaneous microdialysis technique, and then evaluate its in vivo transdermal penetration enhancing properties. Two traditional Chinese medicine active components, namely tetramethylpyrazine and puerarin, were chosen as lipophilic and hydrophilic model drugs, respectively. Firstly, the concentration difference method was employed to measure the in vitro recovery rate and loss of the microdialysis probe, and the in vivo recoveries of two model drugs were determined by using the retrodialysis method. Secondly, the skin pharmacodynamics behaviors of two model drugs were studied after treatment with different concentrations of the essential oil, and the well-established and standard penetration enhancer Azone was selected as a positive control. It was found that the recovery of microdialysis probe was equal to its loss for two model drugs, with no interaction between drugs in dialysis membranes. The retrodialysis studies revealed that the in vivo recovery of tetramethylpyrazine and puerarin were 59.17%, 19.85%, respectively. The skin pharmacodynamics studies showed that the essential oil could facilitate the transdermal absorption of tetramethylpyrazine in a concentration-dependent manner, and the enhancement ratio (ER) for 5% essential oil was 98.64, which was higher than that of the optimum concentration of Azone (3% Azone, ER=89.11). Meanwhile, the Zanthoxyli Pericarpium could effectively promote the transdermal permeation of the puerarin in a concentration-dependent manner. Hence, this study further confirmed that the Zanthoxyli Pericarpium had excellent penetration-enhancing activity as a natural transdermal penetration enhancer, providing data support for its application in traditional Chinese medicine external preparations.

Plasma metabolomic profiling to reveal antipyretic mechanism of Shuang-huang-lian injection on yeast-induced pyrexia rats.

Shuang-huang-lian injection (SHLI) is a famous Chinese patent medicine, which has been wildly used in clinic for the treatment of acute respiratory tract infection, pneumonia, influenza, etc. The existing randomized controlled trial (RCT) studies suggested that SHLI could afford a certain anti-febrile action. However, seldom does research concern the pharmacological mechanisms of SHLI. In the current study, we explored plasma metabolomic profiling technique and selected potential metabolic markers to reveal the antipyretic mechanism of SHLI on yeast-induced pyrexia rat model using UPLC-Q-TOF/MS coupled with multivariate statistical analysis and pattern recognition techniques. We discovered a significant perturbance of metabolic profile in the plasma of fever rats and obvious reversion in SHLI-administered rats. Eight potential biomarkers, i.e. 1) 3-hydeoxybutyric acid, 2) leucine, 3) 16:0 LPC, 4) allocholic acid, 5) vitamin B2, 6) Cys-Lys-His, 7) 18:2 LPC, and 8) 3-hydroxychola-7, 22-dien-24-oic acid, were screened out by OPLS-DA approach. Five potential perturbed metabolic pathways, i.e. 1) valine, leucine, and isoleucine biosynthesis, 2) glycerophospholipid metabolism, 3) ketone bodies synthesis and degradation, 4) bile acid biosynthesis, and 5) riboflavin metabolism, were revealed to relate to the antipyretic mechanisms of SHLI. Overall, we investigated antipyretic mechanisms of SHLI at metabolomic level for the first time, and the obtained results highlights the necessity of adopting metabolomics as a reliable tool for understanding the holism and synergism of Chinese patent drug.