ROS/TRPA1/CGRP signaling mediates cortical spreading depression

Abstract Objectives The transient receptor potential ankyrin A 1 (TRPA1) channel and calcitonin gene-related peptide (CGRP) are targets for migraine prophylaxis. This study aimed to understand their mechanisms in migraine by investigating the role of TRPA1 in cortical spreading depression (CSD) in vivo and exploring how reactive oxygen species (ROS)/TRPA1/CGRP interplay in regulating cortical susceptibility to CSD. Methods Immunohistochemistry was used for detecting TRPA1 expression. CSD was induced by K+ on the cerebral cortex, monitored using electrophysiology in rats, and intrinsic optical imaging in mouse brain slices, respectively. Drugs were perfused into contralateral ventricle of rats. Lipid peroxidation (malondialdehyde, MDA) analysis was used for indicating ROS level. Results TRPA1 was expressed in cortical neurons and astrocytes of rats and mice. TRPA1 deactivation by an anti-TRPA1 antibody reduced cortical susceptibility to CSD in rats and decreased ipsilateral MDA level induced by CSD. In mouse brain slices, H2O2 facilitated submaximal CSD induction, which disappeared by the antioxidant, tempol and the TRPA1 antagonist, A-967079; Consistently, TRPA1 activation reversed prolonged CSD latency and reduced magnitude by the antioxidant. Further, blockade of CGRP prolonged CSD latency, which was reversed by H2O2 and the TRPA1 agonist, allyl-isothiocyanate, respectively. Conclusions ROS/TRPA1/CGRP signaling plays a critical role in regulating cortical susceptibility to CSD. Inhibition ROS and deactivation of TRPA1 channels may have therapeutic benefits in preventing stress-triggered migraine via CGRP

Effect of in vitro gastrointestinal digestion on the chemical composition and antioxidant properties of Ginkgo biloba leaves decoction and commercial capsules

In this study Ginkgo biloba leaves (GBL) decoction and commercial capsules were digested using an in vitro model. Thirty-six active compounds were identified and quantified by HPLC-ESI-MS analysis based on the MS/MS patterns (precursor ions and product ions) and retention times, in comparison with reference standards. Most compounds in GBL showed a significant decrease during intestinal digestion, with an exception of vanillic acid and biflavonoids. Bioaccessibility values of chemical compositions varied between decoction and capsules samples. Also, significant reductions of total flavonoids and total phenolic content was observed after in vitro digestion. Both, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) scavenging capacity decreased after gastric digestion, but increased during intestinal digestion. Nevertheless, different behaviour was observed in reducing antioxidant power (FRAP) assay. Compared to the pH of digestion, the influence of digestive enzymes on the chemical composition and antioxidant activity of GBL was relatively minor. Overall, these results may help provide a valid foundation for further investigations on bioactive compounds and the pharmacodynamics of GBL

Src family kinases activity is required for transmitting purinergic P2X7 receptor signaling in cortical spreading depression and neuroinflammation

BACKGROUND: Purinergic P2X7 receptor plays an important role in migraine pathophysiology. Yet precise molecular mechanism underlying P2X7R signaling in migraine remains unclear. This study explores the hypothesis that P2X7 receptor transmits signaling to Src family kinases (SFKs) during cortical spreading depression (CSD) and neuroinflammation after CSD. METHODS: CSD was recorded using electrophysiology in rats and intrinsic optical imaging in mouse brain slices. Cortical IL-1β and TNFα mRNA levels were detected using qPCR. Glutamate release from mouse brain slices was detected using glutamate assay. RESULTS: The data showed that deactivation of SFKs by systemic injection of PP2 reduced cortical susceptibility to CSD in rats and CSD-induced IL-1β and TNF-α gene expression in rat ipsilateral cortices. Consistently, in mouse brain slices, inhibition of SFKs activity by saracatinib and P2X7 receptor by A740003 similarly reduced cortical susceptibility to CSD. When the interaction of P2X7 receptor and SFKs was disrupted by TAT-P2X7, a marked reduction of cortical susceptibility to CSD, IL-1β gene expression and glutamate release after CSD induction were observed in mouse brain slices. The reduced cortical susceptibility to CSD by TAT-P2X7 was restored by NMDA, and disrupting the Fyn-NMDA interaction using TAT-Fyn (39-57) but not disrupting Src-NMDA receptor interaction using TAT-Src (40-49) reduced cortical susceptibility to CSD. Furthermore, activation of P2X7 receptor by BzATP restored the TAT-Fyn (39-57)-reduced cortical susceptibility to CSD. CONCLUSION: This study reveals that SFKs activity transmits P2X7 receptor signaling to facilitate CSD propagation via glutamatergic pathway and promote neuroinflammation, which is of particular relevance to migraine

GWAS and WGCNA uncover hub genes controlling salt tolerance in maize (Zea mays L.) seedlings

Salt stress influences maize growth and development. To decode the genetic basis and hub genes controlling salt tolerance is a meaningful exploration for cultivating salt-tolerant maize varieties. Herein, we used an association panel consisting of 305 lines to identify the genetic loci responsible for Na+- and K+-related traits in maize seedlings. Under the salt stress, seven significant single nucleotide polymorphisms were identified using a genome-wide association study, and 120 genes were obtained by scanning the linkage disequilibrium regions of these loci. According to the transcriptome data of the above 120 genes under salinity treatment, we conducted a weighted gene co-expression network analysis. Combined the gene annotations, two SNaC/SKC (shoot Na+ content/shoot K+ content)-associated genes GRMZM2G075104 and GRMZM2G333183 were finally identified as the hub genes involved in salt tolerance. Subsequently, these two genes were verified to affect salt tolerance of maize seedlings by candidate gene association analysis. Haplotypes TTGTCCG-CT and CTT were determined as favorable/salt-tolerance haplotypes for GRMZM2G075104 and GRMZM2G333183, respectively. These findings provide novel insights into genetic architectures underlying maize salt tolerance and contribute to the cultivation of salt-tolerant varieties in maize

Prediction of Apple Hybrid Offspring Aroma Based on Hyperspectral

Used Random forest algorithm to construct a prediction model of aroma components based on the hybrid offspring of ‘Honeycrisp’ × ‘Maodi’, and different preprocessing methods were tried (Standardization (SS), First-order Derivative (D1) and Standard normal variate (SNV)). The aroma composition and content were determined by gas chromatography-mass spectrometry (GC-MS), and the main aroma components of apples were classified according to compound categories, including ester, aldehyde, ketone, alcohol. Taking the chemical groups as the research objects, the characteristic wavelengths were selected by grid search algorithm, and the characteristic wavelength-aroma chemical group model was established, and the same method was used to construct the model for single aroma components. The results show: SNV has the best noise removal effect among the five preprocessing methods. Under the SNV treatment, aroma chemical groups of apples showed a good correlation with the spectrum. The number of characteristic spectra of ester are 413, 493, 512, 551, 592, 600, 721, 727, 729, 733 nm, all in the visible light range. The determination coefficient (R2), the root mean square error (RMSE) and the ratio of the standard deviation values (RPD) of validation were 0.90, 4936.16 and 1.13. The characteristic spectrum of alcohols is 519, 562, 570, 571, 660, 676, 737, 738 nm, the range is close to that of ester. The R2 and RMSE of alcohol validation are 0.92 and 83.21, and RPD is 1.30. The number of characteristic spectra of aldehyde is 20, and the most important band is 1000 nm, which is outside the visible light range. The number of characteristic spectra of ketone is 15, and also has some distribution outside the visible light range. The R2 of aldehyde and ketone validation are 0.84 and 0.86. Except for cyclooctanol, the R2 of single aroma compound prediction model performed poorly. Based on the models, we tried to visualize alcohol, which can roughly represent their distribution on apple. Their distributions all show significant differences in the center and edge of apple, but the results are still rough due to the accuracy of models. In conclusion, the study can preliminarily prove that hyperspectral imaging technology (HSI) can perform non-destructive detection of aroma in apple hybrid offspring

Exploration and Optimisation of High-Salt Wastewater Defluorination Process

The typical lime precipitation method is used to treat high-concentration fluorine-containing wastewater. In this way, the fluorine in the wastewater can be removed in the form of CaF2. Thus, this method has a good fluoride removal effect. In this study, calcium hydroxide was used to adjust the pH and achieve a significant fluoride removal effect at the same time. The removal rate of fluoride ion decreases gradually with the increase in the concentration of sulphate in the raw water. When the synergistic defluorination cannot meet the requirements of water production, adding a step of aluminium salt flocculation and precipitation can further reduce the fluoride ion concentration. According to the feasibility of the actual project, this study improves the lime coagulation precipitation defluorination process on this basis, and the combined process is synchronised. In the process optimisation, barium chloride is added to remove the influence of sulphate radicals in the water, and then, the pH is adjusted to 5–6. The fluoride ion concentration in high-salt wastewater can be reduced from 446.6 mg/L to 35.4 mg/L by defluorination after pre-treatment whose removal rate was 92.1%. The combined process synchronously removes fluorine and purifies the water quality to a certain extent. Indicators such as COD, total phosphorus, ammonia nitrogen, and chloride ions in wastewater are reduced, and the removal rate is increased by 35.5% under the same conditions. This scheme improves the wastewater treatment effect without increasing the existing treatment equipment. Thus, it achieves a better defluorination effect and reduces the dosage of chemicals as much as possible, which is conducive to lowering the discharge of sludge after treatment

Effect of in vitro gastrointestinal digestion on the chemical composition and antioxidant properties of Ginkgo biloba leaves decoction and commercial capsules

In this study Ginkgo biloba leaves (GBL) decoction and commercial capsules were digested using an in vitro model. Thirty-six active compounds were identified and quantified by HPLC-ESI-MS analysis based on the MS/MS patterns (precursor ions and product ions) and retention times, in comparison with reference standards. Most compounds in GBL showed a significant decrease during intestinal digestion, with an exception of vanillic acid and biflavonoids. Bioaccessibility values of chemical compositions varied between decoction and capsules samples. Also, significant reductions of total flavonoids and total phenolic content was observed after in vitro digestion. Both, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis (3-ethylbenzothiazo-line-6-sulfonic acid (ABTS) scavenging capacity decreased after gastric digestion, but increased during intestinal digestion. Nevertheless, different behaviour was observed in reducing antioxidant power (FRAP) assay. Compared to the pH of digestion, the influence of digestive enzymes on the chemical composition and antioxidant activity of GBL was relatively minor. Overall, these results may help provide a valid foundation for further investigations on bioactive compounds and the pharmacodynamics of GBL

Sarcoma family kinase activity is required for cortical spreading depression

Objectives Sarcoma family kinase activity is associated with multiple diseases including ischemia and cancer; however, its role in the mechanism of migraine aura has been less well characterised. This study aims to investigate whether sarcoma family kinase is required for cortical spreading depression. Methods Cortical spreading depression was induced by topical application of K+ to the cerebral cortex and was monitored using electrophysiology in rats, and intrinsic optical signal in mouse brain slices. Drugs were perfused into the contralateral cerebral ventricle for pharmacological manipulations in rats. Western blot analysis was used for detecting the level of phosphorylated, and total, sarcoma family kinase in the ipsilateral cortex of rats. Key results The data demonstrate that a single cortical spreading depression in rats induced ipsilateral cortical sarcoma family kinase phosphorylation at the Y416 site. Deactivation of sarcoma family kinase by its inhibitor (3-(4-chlorophenyl) 1-(1,1-dimethylethyl)-1 H-pyrazolo[3,4- dpyrimidin-4-amine) suppressed the elevated enzyme activity and cortical susceptibility to cortical spreading depression. Interestingly, the inhibitory effect of the N-methyl-D-aspartate receptor antagonist NVP-AAM077 on cortical spreading depression was reversed by the sarcoma family kinase activator pYEEI (EPQY(PO3H2)EEEIPIYL), suggesting a link between this enzyme and N-methyl-D-aspartate receptors. Similarly, after deactivation of sarcoma family kinase, a reduction of sarcoma family kinase phosphorylation and cortical susceptibility to cortical spreading depression was observed with NVP-AAM077. Conclusions We conclude that activation of sarcoma family kinase is required for cortical spreading depression, and this process is regulated by recruiting N-methyl-D-aspartate receptors. This study provides novel insight for sarcoma family kinase function in the mechanism of migraine aura. </jats:sec

PROTOCOL: Critical appraisal of methodological quality and reporting items of systematic reviews with meta‐analysis in evidence‐based social science in China: A systematic review

Abstract This is the protocol for a Campbell systematic review. The objectives are as follows: (1) To evaluate the reporting quality of systematic reviews published in Chinese social science journals against the PRISMA and MOOSE standards; (2) To evaluate the methodology quality of systematic reviews published in Chinese social science journals against the AMSTAR‐2 and DART standards; and (3) To analyze other characteristics of systematic reviews published in Chinese social science journals using content analysis