CB2R induces a protective response against epileptic seizures through ERK and p38 signaling pathways.

BACKGROUND AND PURPOSE: Epilepsy is a pivotal neurological disorder characterized by the synchronous discharging of neurons to induce momentary brain dysfunction. Temporal lobe epilepsy is the most common type of epilepsy, with seizures originating from the mesial temporal lobe. The hippocampus forms part of the mesial temporal lobe and plays a significant role in epileptogenesis; it also has a vital influence on the mental development of children. In this study, we aimed to explore the effects of CB2 receptor (CB2R) activation on ERK and p38 signaling in nerve cells of a rat epilepsy model. MATERIALS AND METHODS: We treated Sprague-Dawley rats with pilocarpine to induce an epilepsy model and treated such animals with a CB2R agonist (JWH133) alone or with a CB2R antagonist (AM630). Nissl's stain showed the neuron conditon in different groups. Western blot analyzed the level of p-ERK and p-p38. RESULTS: JWH133 can increase the latent period of first seizure attack and decrease the Grades IV-V magnitude ratio after the termination of SE. Nissl's stain showed JWH133 protected neurons in the hippocampus while AM630 inhibited the functioning of CB2R in neurons. Western blot analysis showed that JWH133 decreased levels of p-ERK and p-p38, which is found at increased levels in the hippocampus of our epilepsy model. In contrast, AM630 inhibited the protective function of JWH133 and also enhanced levels of p-ERK and p-p38. CONCLUSIONS: CB2R activation can induce neurons proliferation and survival through activation of ERK and p38 signaling pathways.

Features of Childhood Arterial Ischemic Stroke in China.

Objective: The aim of this study was to identify the features and risk factors for arterial ischemic stroke (AIS) in children. Methods: We retrospectively analyzed the initial symptoms, clinical manifestations, risk factors, neuroradiological findings, and treatment data of 75 Chinese children aged between 1 month and 14 years (median 5.7 years) who were diagnosed with AIS in our hospital between 2013 and 2018. Results: Among these 75 cases of childhood AIS, 53 patients (70.67%) were male, and the male-to-female ratio was 2.41:1. A total of 55 cases (73.33%) had respiratory tract infection with fever. Seventy cases had lesions in the basal ganglia (46 left, 24 right). All patients were treated conservatively without thrombolytic therapy. Intravenous immunoglobulin treatment was given to children with fever and drowsiness. Conclusion: Infection was an important risk factor for children with AIS in China. Infection and thrombophilia risk factors were more likely to occur in isolation. The stroke lesions commonly occurred in the basal ganglia region.

[Effects of lead stress on net photosynthetic rate, SPAD value and ginsenoside production in Ginseng (Panax ginseng)].

The paper aimed to evaluate the effects of lead stress on photosynthetic performance and ginsenoside content in ginseng (Panax ginseng). To accomplish this, three years old ginseng were cultivated in pot and in phytotron with different concentrations of lead, ranging from 0 to 1000 mg x kg(-1) soil for a whole growth period (about 150 days). The photosynthetic parameters in leaves and ginsenoside content in roots of ginseng were determined in green fruit stage and before withering stage, respectively. In comparison with the control, net photosynthetic rate and SPAD value in ginseng leaves cultivated with 100 and 250 mg x kg(-1) of lead changed insignificantly, however, ginseng supplied with 500 and 1 000 mg x kg(-1) of lead showed a noticeably decline in the net rate of photosynthesis and SPAD value (P < 0.05), the lowest net photosynthetic rate and SPAD value showed in the treatment supplied with 1 000 mg x kg(-1) of lead, with decline of 57.8%,11.0%, respectively. Total content of ginsenoside in ginseng roots cultivated with 100 mg x kg(-1) of lead showed insignificantly change compared to the control, but the content increased remarkably in treatments supplied with 250, 500, 1 000 mg x kg(-1) of lead (P < 0.05), and highest content appeared in these ginsengs exposed to 1000 mg x kg(-1) of lead. The net photosynthetic rate and SPAD value in leaves of ginseng both showed significantly negative linear correlations with lead stress level (P < 0.01), and significant positive linear correlations between total content of ginsenoside and lead concentration was also observed (P < 0.05). These results strongly indicate that exposing to high level of lead negatively affects photosynthetic performance in ginseng leaves, but benefits for accumulation of secondary metabolism (total content of ginsenoside) in ginseng root.

Comparative study of neonatal brain injury fetuses using machine learning methods for perinatal data.

OBJECTIVE: CTG is used to record the fetus's fetal heart rate and uterine contraction signal during pregnancy. The prenatal fetal intrauterine monitoring level can be used to evaluate the fetal intrauterine safety status and reduce the morbidity and mortality of the perinatal fetus. Perinatal asphyxia is the leading cause of neonatal hypoxic-ischemic encephalopathy and one of the leading causes of neonatal death and disability. Severe asphyxia can cause brain and permanent nervous system damage and leave different degrees of nervous system sequelae. METHODS: This paper evaluates the classification performance of several machine learning methods on CTG and provides the auxiliary ability of clinical judgment of doctors. This paper uses the data set on the public database UCI, with 2126 samples. RESULTS: The accuracy of each model exceeds 80%, of which XGBoost has the highest accuracy of 91%. Other models are Random tree (90%), light (90%), Decision tree (83%), and KNN (81%). The performance of the model in other indicators is XGBoost (precision: 90%, recall: 93%, F1 score: 90%), Random tree (precision: 88%, recall: 91%, F1 score: 89%), lightGBM (precision: 87%, recall: 93%, F1 score: 90%), Decision tree (precision: 83%, recall: 86%, F1 score: 84%), KNN (precision: 77%, recall: 85%, F1 score: 81%). CONCLUSION: The performance of XGBoost is the best of all models. This result also shows that using the machine learning method to evaluate the fetus's health status in CTG data is feasible. This will also provide and assist doctors with an objective assessment to assist in clinical diagnosis.

Pharmacological inhibition of ferroptosis as a therapeutic target for sepsis-associated organ damage.

Sepsis is a complex clinical syndrome caused by dysfunctional host response to infection, which contributes to excess mortality and morbidity worldwide. The development of life-threatening sepsis-associated organ injury to the brain, heart, kidneys, lungs, and liver is a major concern for sepsis patients. However, the molecular mechanisms underlying sepsis-associated organ injury remain incompletely understood. Ferroptosis, an iron-dependent non-apoptotic form of cell death characterized by lipid peroxidation, is involved in sepsis and sepsis-related organ damage, including sepsis-associated encephalopathy, septic cardiomyopathy, sepsis-associated acute kidney injury, sepsis-associated acute lung injury, and sepsis-induced acute liver injury. Moreover, compounds that inhibit ferroptosis exert potential therapeutic effects in the context of sepsis-related organ damage. This review summarizes the mechanism by which ferroptosis contributes to sepsis and sepsis-related organ damage. We focus on the emerging types of therapeutic compounds that can inhibit ferroptosis and delineate their beneficial pharmacological effects for the treatment of sepsis-related organ damage. The present review highlights pharmacologically inhibiting ferroptosis as an attractive therapeutic strategy for sepsis-related organ damage.

Effects of a natural prolyl oligopeptidase inhibitor, rosmarinic acid, on lipopolysaccharide-induced acute lung injury in mice.

Rosmarinic acid (RA), a polyphenolic phytochemical, is a natural prolyl oligopeptidase inhibitor. In the present study, we found that RA exerted potent anti-inflammatory effects in in vivo models of acute lung injury (ALI) induced by lipopolysaccharide (LPS). Mice were pretreated with RA one hour before challenge with a dose of 0.5 mg/kg LPS. Twenty-four hours after LPS was given, bronchoalveolar lavage fluid (BALF) was obtained to measure pro-inflammatory mediator and total cell counts. RA significantly decreased the production of LPS-induced TNF-a, IL-6, and IL-1ß compare with the LPS group. When pretreated with RA (5, 10, or 20 mg/kg) the lung wet-to-dry weight (W/D) ratio of the lung tissue and the number of total cells, neutrophils and macrophages in the BALF were decreased significantly. Furthermore, RA may enhance oxidase dimutase (SOD) activity during the inflammatory response to LPS-induced ALI. And we further demonstrated that RA exerts anti-inflammation effect in vivo models of ALI through suppresses ERK/MAPK signaling in a dose dependent manner. These studies have important implications for RA administration as a potential treatment for ALI.

Elevated CO2 enhanced water use efficiency of wheat to progressive drought stress but not on maize.

Global rising atmospheric CO2 concentration ([CO2]) and drought stress exert profound influences on crop growth and yield. The objective of the present study was to investigate the responses of leaf gas exchange and plant water use efficiency (WUE) of wheat (C3) and maize (C4) plants to progressive drought stress under ambient (a[CO2], 400 ppm) and elevated (e[CO2], 800 ppm) atmospheric CO2 concentrations. The fraction of transpirable soil water (FTSW) was used to evaluate soil water status in the pots. Under non-drought stress, e[CO2] increased the net photosynthetic rate (An) solely in wheat, and dry matter accumulation (DMA), whereas it decreased stomatal conductance (g s) and water consumption (WC), resulting in enhanced WUE by 27.82% for maize and 49.86% for wheat. After onset of progressive soil drying, maize plants in e[CO2] showed lower FTSW thresholds than wheat, at which e.g. gs (0.31 vs 0.40) and leaf relative water content (0.21 vs 0.43) starts to decrease, indicating e[CO2] conferred a greater drought resistance in maize. Under the combination of e[CO2] and drought stress, enhanced WUE was solely found in wheat, which is mainly associated with increased DMA and unaffected WC. These varied responses of leaf gas exchange and WUE between the two species to combined drought and e[CO2] suggest that specific water management strategies should be developed to optimize crop WUE for different species in a future drier and CO2-enriched environment.

Shifts in rhizosphere microbial communities in Oplopanax elatus Nakai are related to soil chemical properties under different growth conditions.

Plant growth environment plays an important role in shaping soil microbial communities. To understand the response of soil rhizosphere microbial communities in Oplopanax elatus Nakai plant to a changed growth conditions from natural habitation to cultivation after transplant. Here, a comparative study of soil chemical properties and microbial community using high-throughput sequencing was conducted under cultivated conditions (CT) and natural conditions (WT), in Changbai Mountain, Northeast of China. The results showed that rhizosphere soil in CT had higher pH and lower content of soil organic matter (SOM) and available nitrogen compared to WT. These changes influenced rhizosphere soil microbial communities, resulting in higher soil bacterial and fungi richness and diversity in CT soil, and increased the relative abundance of bacterial phyla Acidobacteria, Chloroflexi, Gemmatimonadetes, Firmicutes and Patescibacteria, and the fungi phyla Mortierellomycota and Zoopagomycota, while decreased bacterial phyla Actinobacteria, WPS-2, Gemmatimonadetes, and Verrucomicrobia, and the fungi phyla Ascomycota, and Basidiomycota. Redundancy analysis analysis indicated soil pH and SOM were the primarily environmental drivers in shaping the rhizosphere soil microbial community in O. elatus under varied growth conditions. Therefore, more attention on soil nutrition management especially organic fertilizer inputs should be paid in O. elatus cultivation.

Maize grain yield enhancement in modern hybrids associated with greater stalk lodging resistance at a high planting density: a case study in northeast China.

Lodging resistance is a critical trait in modern maize breeding. This study aimed to examine maize stalk lodging and its related characteristics in response to increasing planting densities in modern hybrids. A two-year field trial was conducted from 2018 to 2019 with two widely grown commercial hybrids ('Xy335' and 'Fm985') and three planting density treatments of 4.5 × 104 (low density, LD), 6.5 × 104 (medium density, MD), and 8.5 × 104 plants/ha (high density, HD). New hybrid Fm985 had a significantly higher grain yield and lower lodging rate at HD, while there was no significance at LD and MD. Compared to Fm985, old hybrid Xy335 had a significantly high plant height, ear and gravity height, and culm length (CL) across the three planting densities, while opposite stalk bending strength (SBS), dry weight per unit length (DWPU), cross-sectional area, and the cellulose and lignin content in the basal internode were low. Correlation and path analysis revealed that kernel number per ear and lodging rate directly contributed to maize grain yield, while lodging-related traits of SBS, stem lignin, and DWPU had an indirect effect on maize grain yield, suggesting that modern hybrid maize yield enhancement is associated with greater stalk lodging resistance at a high planting density in northeast China.

A novel anti-inflammatory role for ginkgolide B in asthma via inhibition of the ERK/MAPK signaling pathway.

Ginkgolide B is an anti-inflammatory extract of Ginkgo biloba and has been used therapeutically. It is a known inhibitor of platelet activating factor (PAF), which is important in the pathogenesis of asthma. Here, a non-infectious mouse model of asthma is used to evaluate the anti-inflammatory capacity of ginkgolide B (GKB) and characterize the interaction of GKB with the mitogen activated protein kinase (MAPK) pathway. BALB/c mice that were sensitized and challenged to ovalbumin (OVA) were treated with GKB (40 mg/kg) one hour before they were challenged with OVA. Our study demonstrated that GKB may effectively inhibit the increase of T-helper 2 cytokines, such as interleukin (IL)-5 and IL-13 in bronchoalveolar lavage fluid (BALF). Furthermore, the eosinophil count in BALF significantly decreased after treatment of GKB when compared with the OVA-challenged group. Histological studies demonstrated that GKB substantially inhibited OVA-induced eosinophilia in lung tissue and mucus hyper-secretion by goblet cells in the airway. These results suggest that ginkgolide B may be useful for the treatment of asthma and its efficacy is related to suppression of extracellular regulating kinase/MAPK pathway.

[Changes in the hippocampal volume in the acute phase following febrile convulsions in children].

OBJECTIVE: To study the changes in the hippocampal volume in the acute phase after febrile convulsions (FC) in children. METHODS: The brain MRI was performed on 30 children with FC (15 simple and 15 complex) and 30 normal children (control). The hippocampal volume for both sides was compared between groups. RESULTS: In the control group, the average volume of the right hippocampus was significantly larger than that of the left side (P<0.05). There was no significant difference in the hippocampal volume between the left and right sides in the FC group. The average volumes of both the left and right hippocampus in the FC group (2.03 + or - 0.25 cm(3) and 2.18 + or - 0.21 cm(3) respectively) were enlarged compared to the control group (1.90 + or - 0.24 cm(3) and 1.97 + or - 0.20 cm(3) respectively) (P<0.05). There was no significant difference in the hippocampal volume between the simple and the complex FC groups. CONCLUSIONS: The hippocampal volume is enlarged in the acute phase after FC in children. The hippocampal volume in children with simple FC is similar to that in children with complex FC in the acute stage.

Seed Priming with Melatonin Improves the Seed Germination of Waxy Maize under Chilling Stress via Promoting the Antioxidant System and Starch Metabolism.

Chilling stress is one of the major abiotic stresses affecting waxy maize plant growth. Melatonin (MT) is able to improve tolerance to abiotic stress in plants. To investigate the effects of seed priming with MT on tolerance to chilling stress in waxy maize, the seed germination characteristics and physiological parameters were tested with varied MT concentrations (0, 50, 100 µM) and treatment times (12, 24 h) at ambient (25 °C) and chilling (13 °C) temperature. MT primed seeds significantly enhanced the germination potential (by 20.29% and 50.71%, respectively), germination rate (by 20.88% and 33.72%), and increased the radicle length (by 90.73% and 217.14%), hypocotyl length (by 60.28% and 136.14%), root length (by 74.59% and 108.70%), and seed vigor index (46.13%, 63.81%), compared with the non-priming seeds under chilling stress. No significant difference was found in priming time between primed and non-primed seeds. In addition, lower H2O2 and malondialdehyde concentrations, increased antioxidant enzyme activities (superoxide dismutase, peroxidase, catalase and ascorbateperoxidase), and promoted starch metabolism were found in primed seeds compared to non-primed ones. It was suggested that seed priming with MT improved waxy maize seed germination under chilling stress through improving antioxidant system and starch metabolism, which protected from oxidative damage.

Clinical Features of and Risk Factors for Hydrocephalus in Childhood Bacterial Meningitis.

OBJECTIVE: To explore the clinical characteristics of and analyze the risk factors for hydrocephalus in children with bacterial meningitis. METHODS: Retrospective study of a sample of children with bacterial meningitis seen on the pediatric service of Shengjing Hospital of China Medical University between January 1, 2010, and December 31, 2016. RESULTS: Overall, 9.36% (25/267) of patients presented with hydrocephalus. Among patients with hydrocephalus, the age at onset of bacterial meningitis was usually <6 months, 15 patients had confirmed bacterial etiology, and 1 patient died. The most significant results of multivariate analysis for hydrocephalus were a rural living situation, altered level of consciousness, previous treatment with antibiotics, initial cerebrospinal fluid protein >2 g/L, C-reactive protein >100 mg/L, and dexamethasone use. CONCLUSIONS: A severe clinical manifestation and significant laboratory index at admission are the most important predictors of hydrocephalus in children with bacterial meningitis.

CB2R induces a protective response for epileptic seizure via the PI3K 110α-AKT signaling pathway.

Epilepsy is a chronic brain disease caused by abnormal discharging in the brain, which induces momentary brain dysfunction. Cannabinoid 2 receptor (CB2R) is expressed in central nervous system (CNS) and serves an important role in the pathogenesis of CNS diseases. The aim of the present study was to explore the effects of CB2R activation on phosphoinositide 3-kinase (PI3K) 110α-protein kinase B (AKT) signaling in an astrocyte model of epilepsy. Rat CTX TNA2 astrocytes were treated with Mg free solution to establish a cell model of epilepsy and were subsequently treated with a CB2R agonist (JWH133) and antagonist (AM630). Cell cycle analysis revealed that treatment using Mg free solution inhibited cell cycle transition. JWH133 facilitated cell cycle progression while AM630 inhibited it. Western blotting results demonstrated that treatment with Mg free solution downregulated the expression of cyclin D1, cyclin E, phosphorylated Retinoblastoma (p-Rb), B-cell lymphoma 2 (Bcl-2), PI3K 110α, p-AKT and p-mammalian target of rapamycin, whereas JWH133 treatment upregulated these proteins. AM630 ameliorated the JWH133-induced upregulation of these proteins. To confirm the involvement of AKT signaling, the AKT inhibitor wortmannin was used. The results revealed that wortmannin inhibited the effect of JWH133 on p-AKT, cyclin D1, p-Rb and Bcl-2 expression. In addition, the effects of JWH133 and AM630 on PI3K 110α-AKT signaling were verified using a rat model of epilepsy. In conclusion, the present study demonstrates that CB2R activation induces astrocyte proliferation and survival via activation of the PI3K 110α-AKT signaling pathway.

Stomatal Conductance and Morphology of Arbuscular Mycorrhizal Wheat Plants Response to Elevated CO2 and NaCl Stress.

Stomata play a critical role in the regulation of gas exchange between the interior of the leaf and the exterior environment and are affected by environmental and endogenous stimuli. This study aimed to evaluate the effect of the arbuscular mycorrhizal (AM) fungus, Rhizophagus irregularis, on the stomatal behavior of wheat (Triticum aestivum L.) plants under combination with elevated CO2 and NaCl stress. Wheat seedlings were exposed to ambient (400 ppm) or elevated (700 ppm) CO2 concentrations and 0, 1, and 2 g kg-1 dry soil NaCl treatments for 10 weeks. AM symbiosis increased the leaf area and stomatal density (SD) of the abaxial surface. Stomatal size and the aperture of adaxial and abaxial leaf surfaces were higher in the AM than non-AM plants under elevated CO2 and salinity stress. AM plants showed higher stomatal conductance (g s ) and maximum rate of g s to water vapor (g smax ) compared with non-AM plants. Moreover, leaf water potential (Ψ) was increased and carbon isotope discrimination (Δ13C) was decreased by AM colonization, and both were significantly associated with stomatal conductance. The results suggest that AM symbiosis alters stomatal morphology by changing SD and the size of the guard cells and stomatal pores, thereby improving the stomatal conductance and water relations of wheat leaves under combined elevated CO2 and salinity stress.

Licochalcone a inhibits lipopolysaccharide-induced inflammatory response in vitro and in vivo.

Licochalcone A (Lico A), a flavonoid found in licorice root (Glycyrrhiza glabra), is known for its antimicrobial activity and its reported ability to inhibit cancer cell proliferation. In the present study, we found that Lico A exerted potent anti-inflammatory effects in in vitro and in vivo models induced by lipopolysaccharide (LPS). The concentrations of TNF-α, interleukin (IL)-6, and IL-1ß in the culture supernatants of RAW 264.7 cells were determined at different time points following LPS administration. LPS (0.5 mg/kg) was instilled intranasally (i.n.) in phosphate-buffered saline to induce acute lung injury, and 24 h after LPS was given, bronchoalveolar lavage fluid was obtained to measure pro-inflammatory mediator and total cell counts. The phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) p65 protein was analyzed by Western blotting. Our results showed that Lico A significantly reduced the amount of inflammatory cells, the lung wet-to-dry weight (W/D) ratio, protein leakage, and myeloperoxidase activity and enhances oxidase dimutase activity in mice with LPS-induced acute lung injury (ALI). Enzyme-linked immunosorbent assay results indicated that Lico A can significantly down-regulate TNF-α, IL-6, and IL-1ß levels in vitro and in vivo, and treatment with Lico A significantly attenuated alveolar wall thickening, alveolar hemorrhage, interstitial edema, and inflammatory cells infiltration in mice with ALI. In addition, we further demonstrated that Lico A exerts an anti-inflammation effect in an in vivo model of acute lung injury through suppression of NF-κB activation and p38/ERK MAPK signaling in a dose-dependent manner.

Effects of an anthraquinone derivative from Rheum officinale Baill, emodin, on airway responses in a murine model of asthma.

Emodin is a component from traditional Chinese herbal medicines. We focused on investigating whether emodin possesses distinct anti-inflammatory activity on a non-infectious mouse model of asthma, and we aimed to elucidate its involvement with the NF-κB pathway. BALB/c mice that were sensitized and challenged to ovalbumin were treated with emodin (40 mg/kg) 1h before they were challenged with OVA. Our study demonstrated that emodin inhibited OVA-induced increases in eosinophil count; interleukin (IL)-4, IL-5, and IL-13 levels were recovered in bronchoalveolar lavage fluid and reduced serum levels of OVA-specific IgE, IgG, and IgG1. Histological studies demonstrated that emodin substantially inhibited OVA-induced eosinophilia in lung tissue and mucus hyper-secretion by goblet cells in the airway. Furthermore, pretreatment with emodin resulted in a significant reduction in mRNA expression of acidic mammalian chitinase (AMCase), chitinase 3-like protein 4 (Ym2) and Muc5ac in lung tissues and airway hyperresponsiveness to methacholine. These findings suggest that emodin may effectively delay the progression of airway inflammation and could be used as a therapy for patients with allergic airway inflammation.