Biopolymer Hydrogel-Based Salt-Resistant Evaporator for Solar-Energy-Driven Desalination and Water Purification.

Interfacial solar steam generation (ISSG) has recently received much attention as a low-carbon-footprint and high-energy-efficient strategy for seawater desalination and wastewater treatment. However, achieving the goals of a high evaporation rate, ecofriendliness, and high tolerance to salt ions in brine remains a bottleneck. Herein, a novel hydrogel-based evaporator for effective solar desalination was synthesized on the basis of sodium alginate (SA) and carboxymethyl chitosan (CMCS) incorporating a carbon nanotube (CNT)-wrapped melamine sponge (MS) through a simple dipping-drying-cross-linking process. The hydrogel-based evaporator reaches a high evaporation rate of 2.18 kg m-2 h-1 in 3.5 wt % brine under 1 sun irradiation. Furthermore, it demonstrated excellent salt ion rejection in high-concentration salt water. Simultaneously, it exhibits excellent purification functionality toward heavy metals and organic dyes. This study provides a simple and efficient strategy for seawater desalination and wastewater treatment.

Pimpinellin ameliorates macrophage inflammation by promoting RNF146-mediated PARP1 ubiquitination.

Macrophage inflammation plays a central role during the development and progression of sepsis, while the regulation of macrophages by parthanatos has been recently identified as a novel strategy for anti-inflammatory therapies. This study was designed to investigate the therapeutic potential and mechanism of pimpinellin against LPS-induced sepsis. PARP1 and PAR activation were detected by western blot or immunohistochemistry. Cell death was assessed by flow cytometry and western blot. Cell metabolism was measured with a Seahorse XFe24 extracellular flux analyzer. C57, PARP1 knockout, and PARP1 conditional knock-in mice were used in a model of sepsis caused by LPS to assess the effect of pimpinellin. Here, we found that pimpinellin can specifically inhibit LPS-induced macrophage PARP1 and PAR activation. In vitro studies showed that pimpinellin could inhibit the expression of inflammatory cytokines and signal pathway activation in macrophages by inhibiting overexpression of PARP1. In addition, pimpinellin increased the survival rate of LPS-treated mice, thereby preventing LPS-induced sepsis. Further research confirmed that LPS-induced sepsis in PARP1 overexpressing mice was attenuated by pimpinellin, and PARP1 knockdown abolished the protective effect of pimpinellin against LPS-induced sepsis. Further study found that pimpinellin can promote ubiquitin-mediated degradation of PARP1 through RNF146. This is the first study to demonstrate that pimpinellin inhibits excessive inflammatory responses by promoting the ubiquitin-mediated degradation of PARP1.

Myricanol attenuates sepsis-induced inflammatory responses by nuclear factor erythroid 2-related factor 2 signaling and nuclear factor kappa B/mitogen-activated protein kinase pathway via upregulating Sirtuin 1.

Sepsis, a life-threatening condition characterized by dysregulated immune responses, remains a significant clinical challenge. Myricanol, a natural compound, plays a variety of roles in regulating lipid metabolism, anti-cancer, anti-neurodegeneration, and it could act as an Sirtuin 1 (SIRT1) activator. This study aimed to explore the therapeutic potential and underlying mechanism of myricanol in the lipopolysaccharide (LPS)-induced sepsis model. In vivo studies revealed that myricanol administration significantly improved the survival rate of LPS-treated mice, effectively mitigating LPS-induced inflammatory responses in lung tissue. Furthermore, in vitro studies demonstrated that myricanol treatment inhibited the expression of pro-inflammatory cytokines, attenuated signal pathway activation, and reduced oxidative stress in macrophages. In addition, we demonstrated that myricanol selectively enhances SIRT1 activation in LPS-stimulated macrophages, and all of the protective effect of myricanol were reversed through SIRT1 silencing. Remarkably, the beneficial effects of myricanol against LPS-induced sepsis were abolished in SIRT1 myeloid-specific knockout mice, underpinning the critical role of SIRT1 in mediating myricanol's therapeutic efficacy. In summary, this study provides significant evidence that myricanol acts as a potent SIRT1 activator, targeting inflammatory signal pathways and oxidative stress to suppress excessive inflammatory responses. Our findings highlight the potential of myricanol as a novel therapeutic agent for the treatment of LPS-induced sepsis.

Simultaneous Extraction and Determination of Lignans from Schisandra chinensis (Turcz.) Baill. via Diol-Based Matrix Solid-Phase Dispersion with High-Performance Liquid Chromatography.

The quality of Schisandra chinensis (Turcz.) Baill. (S. chinensis) is principally attributed to lignan compounds. In this paper, a simple and rapid strategy for simultaneous extraction and determination of 10 lignans from S. chinensis was established through matrix solid-phase dispersion (MSPD) assisted by diol-functionalized silica (Diol). The experimental parameters for MSPD extraction were screened using the response surface methodology (RSM). Diol (800 mg) was used as a dispersant and methanol (MeOH, 85%, v/v) as an eluting solvent (10 mL), resulting in a high extraction efficiency. MSPD extraction facilitated the combination of extraction and purification in a single step, which was less time-consuming than and avoided the thermal treatment involved in traditional methods. The simultaneous qualification and quantification of 10 lignans was achieved by combining MSPD and high-performance liquid chromatography (HPLC). The proposed method offered good linearity and a low limit of detection starting from 0.04 (schisandrin C) to 0.43 µg/mL (schisantherin B) for lignans, and the relative standard deviation (RSD, %) values of precision were acceptable, with a maximum value of 1.15% (schisantherin B and schisanhenol). The methodology was successfully utilized to analyze 13 batches of S. chinensis from different cultivated areas of China, which proved its accuracy and practicability in the quantitative analysis of the quality control of S. chinensis.

Study on Mechanism of Ginkgo biloba L. Leaves for the Treatment of Neurodegenerative Diseases Based on Network Pharmacology.

Ginkgo biloba L. leaves (GBLs), as widely used plant extract sources, significantly improve cognitive, learning and memory function in patients with dementia. However, few studies have been conducted on the specific mechanism of Neurodegenerative diseases (NDs). In this study, network pharmacology was employed to elucidate potential mechanism of GBLs in the treatment of NDs. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to obtain the chemical components in accordance with the screening principles of oral availability and drug-like property. Potential targets of GBLs were integrated with disease targets, and intersection targets were exactly the potential action targets of GBLs for treating NDs; these key targets were enriched and analyzed by the protein protein interaction (PPI) analysis and molecular docking verification. Key genes were ultimately used to find the biological pathway and explain the therapeutic mechanism by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Twenty-seven active components of GBLs may affect biological processes such as oxidative reactions and activate transcription factor activities. These components may also affect 120 metabolic pathways, such as the PI3K/AKT pathway, by regulating 147 targets, including AKT1, ALB, HSP90AA1, PTGS2, MMP9, EGFR and APP. By using the software iGEMDOCK, the main target proteins were found to bind well to the main active components of GBLs. GBLs have the characteristics of multi-component and multi-target synergistic effect on the treatment of NDs, which preliminarily predicted its possible molecular mechanism of action, and provided the basis for the follow-up study.

A novel online preparative high-performance liquid chromatography system with the multiple trap columns-valve switch technique for the rapid and efficient isolation of main flavonoids from Epimedium koreanum Nakai.

In this work, a new online preparative high-performance liquid chromatography was developed for the fast and efficient separation of complex chemical mixtures from natural products. This system integrates two chromatographic systems into an online automatic separation system using the technique of multiple trap columns with valve switching. The sample was first separated into 18 subfractions in the online preparative high-performance liquid chromatography, and the sample eluents were then diluted and captured online on 18 trap columns by the multiple trap columns technique, respectively. Each subfraction retained on the trap column was transferred online to the separation column for the second separation. Finally, the target compounds were purified by appropriate separation conditions and multiple heart-cutting strategies. Importantly, the system was successfully used to separate 18 high-purity flavonoids from the crude extract of Epimedium koreanum Nakai online in one step. The entire separation time was approximately 20 h, and the structures were characterized by the high-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry and nuclear magnetic resonance. This online preparative high-performance liquid chromatography system represents an efficient and rapid separation system that has the potential for a wide array of applications in the separation of complex chemical components from natural products.

[Research progress on pathogenesis of ischemic stroke and traditional Chinese medicine commonly used for treatment of ischemic stroke].

Stroke has become the second leading cause of death in the world, and the most common type is the ischemic stroke. Due to its rapid onset and complex conditions, ischemic stroke is a major neurological disorder that causes disability. Ischemic stroke mainly results from atherosclerosis, and the pathogenesis of ischemic stroke mainly includes energy metabolism disorders in the brain, the toxicity of excitatory amino acids, oxidative/nitrification stress, inflammatory response, apoptosis, and autophagy. With the characteristics of multi-component and multi-target, traditional Chinese medicine could be used to treat ischemic stroke at different stages. This article summarized the latest research progress on the pathogenesis of ischemic stroke and commonly used traditional Chinese medicine for treatment of ischemic stroke in order to provide references for the further research and clinical treatment of ischemic stroke.

Isolation and enrichment of Ginkgo biloba extract by a continuous chromatography system.

In this study, an effective method was developed for the isolation and enrichment of Ginkgo biloba extract by continuous chromatography system. The adsorption and desorption ratio of flavonoids as main index, the best macroporous resin was screened out from six resins by static adsorption and desorption tests. At the same time the adsorption and desorption parameters were optimized by dynamic adsorption and desorption tests. Under optimal parameters, five operations consisting of loading, washing, desorbing, regenerating, and balancing were integrated across the continuous chromatography system for the purpose of refining 66 L of crude extract solution. The results were as follows, 198.22 g of Ginkgo biloba extracts was produced, which contained 65.83 g of flavonoids and 15.44 g of lactones. The content of flavonoids and lactones increased from 2.76 and 0.72% in the crude extract to 33.21 and 7.79%, with a recovery yield of 91.26 and 81.21%. Methodology validation showed that the proposed method had high stability and reproducibility. Compared with the traditional macroporous resin method, the proposed method had a short processing time and low solvent consumption. Our studies indicated that the newly developed method is an effective procedure for the isolation and enrichment of Ginkgo biloba extract.

A systems-level approach for investigating organophosphorus pesticide toxicity.

The full understanding of the single and joint toxicity of a variety of organophosphorus (OP) pesticides is still unavailable, because of the extreme complex mechanism of action. This study established a systems-level approach based on systems toxicology to investigate OP pesticide toxicity by incorporating ADME/T properties, protein prediction, and network and pathway analysis. The results showed that most OP pesticides are highly toxic according to the ADME/T parameters, and can interact with significant receptor proteins to cooperatively lead to various diseases by the established OP pesticide -protein and protein-disease networks. Furthermore, the studies that multiple OP pesticides potentially act on the same receptor proteins and/or the functionally diverse proteins explained that multiple OP pesticides could mutually enhance toxicological synergy or additive on a molecular/systematic level. To the end, the integrated pathways revealed the mechanism of toxicity of the interaction of OP pesticides and elucidated the pathogenesis induced by OP pesticides. This study demonstrates a systems-level approach for investigating OP pesticide toxicity that can be further applied to risk assessments of various toxins, which is of significant interest to food security and environmental protection.

Phytochemical and biological investigations of Amaryllidaceae alkaloids: a review.

Amaryllidaceae is a family that includes 75 genera and about 1100 species, which have a long history of medicinal use. Many plants have been proven to possess efficacy for neurological injury and inflammatory conditions. This article summarizes 357 Amaryllidaceae alkaloids, and cites 166 174 references over the last three decades. These alkaloids are classified into 14 skeleton types, and their abundant sources are also included. Modern pharmacology studies demonstrate that alkaloids that exclusively occur in Amaryllidaceae plant possess wide-ranging pharmacological actions, especially effects on the central nervous system, as well as antitumor, antimicrobial, and anti-inflammatory activities. Effective monomeric compounds from Amaryllidaceae screened for pharmacological activity in vivo and in vitro are also summarized.

Parent/caregiver reported health-related functioning in Chinese children with epilepsy: A cross-sectional, parents-responded, hospital-based study.

Due to epilepsy, children have faced several difficulties and challenges. Epilepsy shows an impact on a person quality of life (QoL) which can be associated with psychological, physical, and social aspects and can have a greater impact on the QoL of the person than that do through another chronic disease(s). Health-related quality of life (HRQoL) is a multidimensional concept that includes emotional, mental, physical, behavioral, and social aspects of the well-being and functioning of the patients. The objective of the study was to assess the level of HRQoL for childhood epilepsy in Chinese children under treatment for epilepsy. Also, to identify factors that can affect QoL. A descriptive, cross-sectional, parents-responded questionnaire-based study was performed on 382, 4 to 18 years old hospitalized and outpatient units' children from various backgrounds, varying socio-economic status, and of varying intellectual capability with the most recent epilepsy. The clinical and socio-demographic parameters were collected from medical records and by an interview with parents of children. The quality of life in the children with epilepsy (QoLCE) questionnaire-91 was used to access HRQoL. The average age of children was 10.4 ±â€…3.2 years. The duration of epilepsy in children was 3.90 ±â€…2.80 years. Among the enrolled children, 153 (40%) children were girls, and 229 (60%) individuals were boys. The overall QoLCE questionnaire-91 score was 69.40 ±â€…16.40 (minimum scores: 27.80, maximum scores: 87.80). A total of 324 (84%), 41 (11%), and 17 (5%) children were from urban, suburban, and rural types, respectively. The generalized seizure (198 (52%)) is the most common type of existing seizure followed by focal seizure (152 (40%)). Male (P = .015), older children (12-14 years, P = .019), those residing in urban areas (P = .021), and those with focal seizures (P = .049) had higher QoL scores. The overall QoL of Chinese CWE is affected by sex, age, urbanization, and seizure type but not with education or economic status of the families. The study provides helpful insight for the clinicians in the management of chronic childhood epileptic conditions (Level of Evidence: II; Technical Efficacy Stage: 5).

[Simultaneous determination of five lignans from Schisandra chinensis by matrix solid-phase dispersion extraction-high performance liquid chromatography].

The kidney-shaped, red-colord fruit from the plant, Schisandra chinensis (Turcz.) Baill, which belongs to the Schisandraceae family, is among the most popular remedies used in traditional Chinese medicine. The English name of the plant is "Chinese magnolia vine". It has been used in Asia since ancient times to treat a variety of ailments, including chronic cough and dyspnea, frequent urination, diarrhea, and diabetes. This is because of the wide range of bioactive constituents, such as lignans, essential oils, triterpenoids, organic acids, polysaccharides, and sterols. In some cases, these constituents affects the pharmacological efficacy of the plant. Lignans with a dibenzocyclooctadiene-type skeleton are considered to be the major constituents and main bioactive ingredients of Schisandra chinensis. However, because of the complex composition of Schisandra chinensis, the extraction yields of lignans are low. Thus, it is particularly important to study pretreatment methods used during sample preparation for the quality control of traditional Chinese medicine. Matrix solid-phase dispersion extraction (MSPD) is a comprehensive process involving destruction, extraction, fractionation, and purification. The MSPD method is simple, it requires only a small number of samples and solvents, it does not require any special experimental equipments or instruments, and it can be used to prepare liquid, viscous, semi-solid, solid samples. In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. The target compounds were separated on a C18 column with a gradient elution of 0.1% (v/v) formic acid aqueous solution and acetonitrile as the mobile phases, and detection was performed at a wavelength of 250 nm. First, the effects of 12 adsorbents, including silica gel, acidic alumina, neutral alumina, alkaline alumina, Florisil, Diol, XAmide, Xion, and the inverse adsorbents, C18, C18-ME, C18-G1, and C18-HC, on the extraction yields of lignans were investigated. Second, effects of the mass of the adsorbent, the type of eluent, and volume of eluent on the extraction yields of lignans were investigated. Xion was chosen as an adsorbent for MSPD-HPLC analysis of lignans from Schisandra chinensis. Optimization of the extraction parameters showed that the MSPD method had a high lignan extraction yield with Schisandra chinensis powder (0.25 g) as a fixed value, Xion as the adsorbent (0.75 g), and methanol as the elution solvent (15 mL). Analytical methods were developed for five lignans from Schisandra chinensis and these methods showed good linearity (correlation coefficients (R2)≥ 0.9999) for each target analyte. The limits of detection and quantification ranged from 0.0089 to 0.0294 µg/mL and 0.0267 to 0.0882 µg/mL, respectively. Lignans were tested at low, medium, and high levels. The average recovery rates were 92.2% to 111.2%, and the relative standard deviations were 0.23% to 3.54%. Both intra-day and inter-day precisions were less than 3.6%. Compared with hot reflux extraction and ultrasonic extraction methods, MSPD has the advantages of combined extraction and purification, being less time-consuming, and requiring lower solvent volumes. Finally, the optimized method was successfully applied to analyze five lignans from Schisandra chinensis samples from 17 cultivation areas.

Isolation and purification of 12 flavonoid glycosides from Ginkgo biloba extract using sephadex LH-20 and preparative high-performance liquid chromatography.

An efficient and rapid preparative method for the separation and purification of flavonoid glycosides from the Ginkgo biloba extract (GBE) was developed by sephadex LH-20 and preparative high-performance liquid chromatography (HPLC). 40 g GBE of 24% flavonoids were loaded onto the sephadex LH-20 column and five fractions (1.15, 2.57, 1.32, 4.45, and 3.31 g) at flavonoid content of 72.3, 54.2, 63.5, 51.2, and 59.2% were produced. Ultimately, 12 flavonoid glycosides that are at least purities of 97.7% were obtained from 100 mg of each fraction by preparative HPLC. The fraction A, B, and D each contained two flavonoids, yielded 35, 30, 23, 20, 25, and 25 mg, respectively. The fraction C and E each contained three flavonoids, produced 20, 13, 15, 18, 15, and 20 mg, respectively. The chemical structures of the purified compounds were identified by nuclear magnetic resonance (NMR) and electrospray ionization mass spectrometry (ESI/MS).

The Efficacy and Safety of Bivalirudin Versus Heparin in the Anticoagulation Therapy of Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis.

Background: Bivalirudin is a direct thrombin inhibitor (DTI) that can be an alternative to unfractionated heparin (UFH). The efficacy and safety of bivalirudin in anticoagulation therapy in extracorporeal membrane oxygenation (ECMO) remain unknown. Methods: This study followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. A systematic literature search was performed in PubMed, EMBASE, and The Cochrane Library databases to identify all relevant original studies estimating bivalirudin's efficacy and safety versus UFH as anticoagulation therapy in ECMO. The time limit for searching is from the search beginning to June 2021. Two researchers independently screened the literature, extracted data and evaluated the risk of bias of the included studies. The meta-analysis (CRD42020214713) was performed via the RevMan version 5.3.5 Software and STATA version 15.1 Software. Results: Ten articles with 847 patients were included for the quantitative analysis. Bivalirudin can significantly reduce the incidence of major bleeding in children (I 2 = 48%, p = 0.01, odd ratio (OR) = 0.17, 95% confidence interval (CI): 0.04-0.66), patient thrombosis (I 2 = 0%, p = 0.02, OR = 0.58, 95% CI: 0.37-0.93), in-circuit thrombosis/interventions (I 2 = 0%, p = 0.0005, OR = 0.40, 95% CI: 0.24-0.68), and in-hospital mortality (I 2 = 0%, p = 0.007, OR = 0.64, 95% CI: 0.46-0.88). Also, comparable clinical outcomes were observed in the incidence of major bleeding in adults (I 2 = 48%, p = 0.65, OR = 0.87, 95% CI: 0.46-1.62), 30-day mortality (I 2 = 0%, p = 0.61, OR = 0.83, 95% CI: 0.41-1.68), and ECMO duration in adults (I 2 = 41%, p = 0.75, mean difference (MD) = -3.19, 95% CI: -23.01-16.63) and children (I 2 = 76%, p = 0.65, MD = 40.33, 95% CI:-135.45-216.12). Conclusions: Compared with UFH, bivalirudin can be a safe and feasible alternative anticoagulant option to UFH as anticoagulation therapy in ECMO, especially for heparin resistance (HR) and heparin-induced thrombocytopenia (HIT) cases.

Systems pharmacology-based drug discovery and active mechanism of natural products for coronavirus pneumonia (COVID-19): An example using flavonoids.

BACKGROUND: Recently, the value of natural products has been extensively considered because these resources can potentially be applied to prevent and treat coronavirus pneumonia 2019 (COVID-19). However, the discovery of nature drugs is problematic because of their complex composition and active mechanisms. METHODS: This comprehensive study was performed on flavonoids, which are compounds with anti-inflammatory and antiviral effects, to show drug discovery and active mechanism from natural products in the treatment of COVID-19 via a systems pharmacological model. First, a chemical library of 255 potential flavonoids was constructed. Second, the pharmacodynamic basis and mechanism of action between flavonoids and COVID-19 were explored by constructing a compound-target and target-disease network, targets protein-protein interaction (PPI), MCODE analysis, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. RESULTS: In total, 105 active flavonoid components were identified, of which 6 were major candidate compounds (quercetin, epigallocatechin-3-gallate (EGCG), luteolin, fisetin, wogonin, and licochalcone A). 152 associated targets were yielded based on network construction, and 7 family proteins (PTGS, GSK3ß, ABC, NOS, EGFR, and IL) were included as central hub targets. Moreover, 528 GO items and 178 KEGG pathways were selected through enrichment of target functions. Lastly, molecular docking demonstrated good stability of the combination of selected flavonoids with 3CL Pro and ACEⅡ. CONCLUSION: Natural flavonoids could enable resistance against COVID-19 by regulating inflammatory, antiviral, and immune responses, and repairing tissue injury. This study has scientific significance for the selective utilization of natural products, medicinal value enhancement of flavonoids, and drug screening for the treatment of COVID-19 induced by SARS-COV-2.

Dual-Layer Multichannel Hydrogel Evaporator with High Salt Resistance and a Hemispherical Structure toward Water Desalination and Purification.

Interfacial solar steam generation technology has been considered as one of the most promising methods for seawater desalination. However, in practical applications, salt precipitation on the evaporation surface reduces the evaporation rate and impairs long-term stability. Herein, a dual-layer hydrogel-based evaporator that contains a microchannel-structured water-supplying layer and a nanoporous light-absorbing layer was synthesized via sol-gel transition and "hot-ice" template methods. Contributed by the designed structure-induced accelerated salt ion exchange, the hemispherical dual-layer hydrogel evaporator showed excellent salt formation resistance property, as well as a high evaporation rate reaching 2.03 kg m-2 h-1 even under high brine concentration conditions. Furthermore, the hydrogel-based evaporator also demonstrated excellent ion rejection, high/low pH tolerance, and excellent purification properties toward heavy metals and organic dyes. It is believed that this type of dual-layer multichannel evaporator is promising to be used in seawater desalination, water pollution treatment, and other environmental remediation-related applications.

7-Methoxyisoflavone suppresses vascular endothelial inflammation by inhibiting the expression of endothelial adhesion molecules.

Endothelial cells (ECs) are vital regulators of inflammatory processes, there is the potential for inhibition of EC inflammation to be a therapeutic target in chronic inflammatory diseases. This study aimed to investigate the effect of 7-methoxyisoflavone (7-Mif) on endothelial inflammation. Our results showed that 7-Mif have no cytotoxicity on HUVECs. Pretreatment with 5 µM, 10 µM and 50 µM 7-Mif significantly reduced IL-1ß-induced ICAM-1 (28.1% ± 4.1%, 25.9 ± 2.5% and 32.0% ± 3.2%, respectively) and VCAM-1 (48.0% ± 5.6%, 40.1 ± 3.1% and 39.6% ± 3.1%, respectively) mRNA expression. And pretreatment with 10 µM and 50 µM 7-Mif significantly reduced IL-1ß-induced ICAM-1 (45.1% ± 4.4% and 33.6 ± 4.4%, respectively) and VCAM-1 (53.0% ± 3.7% and 53.7 ± 5.1%, respectively) protein levels. Furthermore, pretreatment with 50 µM 7-Mif inhibited monocyte-endothelial cell adhesion (50.2% ± 4.2%). Mechanistically, our results showed that 7-Mif reversed IL-1ß-induced NF-κB activation and p65 translocation to the nucleus, therefore inhibiting endothelial cell inflammation. In addition, we confirmed that 7-Mif 10 mg/kg and 20 mg/kg reduced LPS-induced ICAM-1 (47.3% ± 1.3% and 39.0% ± 3.2%, respectively) and VCAM-1 (56.5 ± 2.8% and 47.8 ± 4.3%, respectively) expression and attenuated inflammatory injury in mice. In conclusion, we showed the inhibitory effect of 7-Mif on endothelial inflammation by suppressing the expression of endothelial adhesion molecules and monocyte adhesion. Our data illustrated that 7-Mif could positively regulate the process of endothelial inflammation.

[Study on chemical changes of salvianolic acid B and lithospermic acid aqueous under conditions of high temperature and high pressure].

OBJECTIVE: To study the chemical changes of salvianolic acid B and lithospermic acid of Salvia miltiorrhiza under the conditions of high temperature and high pressure and explore the reaction mechanism. METHOD: S. miltiorrhiza extracts, salvianolic acid B and lithospermic acid were put in the reactor under the conditions of high temperature and high pressure (120 degrees C, 0.2 MPa), and the chemical changes and stability was studied. RESULT: Salvianolic acid A was the primary product in salvianolic acid B and lithospermic acid's conversion process, and lithospermic acid was an intermediate in the conversion process of salvianolic acid B. Compared with salvianolic acid B, lithospermic acid could convert into more salvianolic acid A and fewer other products in the same conditions. Salvianolic acid A was not stable under the conditions of high temperature and high pressure, and could sequentially convert into other small molecules. CONCLUSION: Referring to the chemical conversion of salvianolic acid B and lithospermic acid, a method of large-scale preparation of salvianolic acid A can be developed.

A RNA-seq approach for exploring the protective effect of ginkgolide B on glutamate-induced astrocytes injury.

ETHNOPHARMACOLOGICAL RELEVANCE: There is substantial experimental evidence to support the view that Ginkgo biloba L. (Ginkgoaceae), a traditional Chinese medicine known to treating stroke, has a protective effect on the central nervous system and significantly improves the cognitive dysfunction caused by disease, including alzheimer disease (AD), vascular dementia, and diabetic encephalopathy. Although a number of studies have reported that ginkgolide B (GB), a diterpenoid lactone compound extracted from Ginkgo biloba leaves, has neuroprotective effects, very little research has been performed to explore its potential pharmacological mechanism on astrocytes under abnormal glutamate (Glu) metabolism in the pathological environment of AD. AIM OF THE STUDY: We investigated the protective effect and mechanism of GB on Glu-induced astrocytes injury. METHODS: Astrocytes were randomly divided into the control group, Glu group, GB group, and GB + IWP-4 group.The CCK-8 assay was used to determine relative cell viability in vitro. Furthermore, RNA sequencing (RNA-seq) was performed to assess the preventive effects of GB in the Glu-induced astrocyte model and reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to validate the possible molecular mechanisms. The effects of GB on the Glu transporter and Glu-induced apoptosis of astrocytes were studied by RT-qPCR and western blot. RESULTS: GB attenuated Glu-induced apoptosis in a concentration-dependent manner, while the Wnt inhibitor IWP-4 reversed the protective effect of GB on astrocytes. The RNA-seq results revealed 4,032 differential gene expression profiles; 3,491 genes were up-regulated, and 543 genes were down-regulated in the GB group compared with the Glu group. Differentially expressed genes involved in a variety of signaling pathways, including the Hippo and Wnt pathways have been associated with the development and progression of AD. RT-qPCR was used to validate 14 key genes, and the results were consistent with the RNA-seq data. IWP-4 inhibited the regulation of GB, disturbed the apoptosis protective effect on astrocytes, and promoted Glu transporter gene and protein expression caused by Glu. CONCLUSION: Our findings demonstrate that GB may play a protective role in Glu-induced astrocyte injury by regulating the Hippo and Wnt pathways. GB was closely associated with the Wnt pathway by promoting expression of the Glu transporter and inhibiting Glu-induced injury in astrocytes.

3-Bromopyruvate decreased kidney fibrosis and fibroblast activation by suppressing aerobic glycolysis in unilateral ureteral obstruction mice model.

AIMS: Enhanced aerobic glycolysis is a motivation of fibroblast-myofibroblast transdifferentiation (FMT), leading to kidney fibrosis. 3-Bromopyruvate (3-BrPA) is a glycolysis inhibitor and has fibrosis-protected effect in liver. This study aims to explore the effects of 3-BrPA on aerobic glycolysis and kidney fibrosis in a unilateral ureteral obstruction (UUO) mice model and transforming growth factor-ß1(TGF-ß1)-stimulated normal rat kidney fibroblast (NRK49F) cell model in vitro. MAIN METHODS: In vivo UUO mouse model and in vitro TGF-ß1 stimulated cell model were built. Immunohistochemical staining, Western blots, Real-time PCR and fluorescence microscopy were employed to detect extra cellular matrix (ECM) synthesis, fibroblast activation, aerobic glycolysis switch and related signaling pathways. KEY FINDINGS: HE and Masson's Trichrome staining showed that 3-BrPA substantially suppressed kidney injury and interstitial collagen production. 3-BrPA also attenuated ECM accumulation in a dose-dependent manner, as shown by immunohistochemistry staining, RT-PCR and western blot. Furthermore, 3-BrPA inhibited FMT, as indicated by α-SMA and PCNA immunofluorescence double staining. Additionally, the results of MTT assay indicated 3-BrPA prevented TGF-ß1 induced fibroblasts proliferation in a time- and dose-dependent manner. Mechanistically, molecular docking results showed that 3-BrPA effectively decreased the aerobic glycolysis related enzymes Hexokinase-2 (HK-2), Lactate dehydrogenase A (LDHA) and Pyruvate kinase isozymes M2 (PKM-2), as well as inhibited IL-1 receptor-associated kinase 4 (IRAK4)/MYC protein levels. SIGNIFICANCE: Our study highlighted that 3-BrPA is a potential reno-protective agent in kidney fibrosis through the inhibition of fibroblasts aerobic glycolysis might via IRAK4/MYC signal pathways.