Successful Treatment of Severe Case of Lipid Overload Syndrome with Pancreatitis and Pneumonia: A Case Report.

Background: Fat overload syndrome is a rare and severe adverse reaction triggered by the infusion of a single source of lipid emulsion, resulting in elevated blood triacylglycerol (TG) levels. The majority of literature reports focus on cases of fat overload syndrome in patients with mild symptoms. This case is significant because it demonstrates the diagnostic and therapeutic experience and provide valuable insights for the management for severe fat overload syndrome. Case Presentation: We present a case report of a female patient who developed fat overload syndrome following prolonged and excessive infusion of lipid emulsion after colon resection surgery. In the setting of compromised immune function and malnutrition, the patient's pulmonary infection and respiratory distress symptoms have further exacerbated. Hence, in addition to severe pancreatitis, the patient has also contracted severe pneumonia. Upon admission, tracheal intubation, plasma exchange and blood perfusion were performed. Subsequently, comprehensive treatment was provided, including anti-infection, antispasmodic, acid suppression, enzyme inhibition, as well as targeted supportive measures to stabilize electrolytes and nutritional status. After treatment, there was a progressive reduction in blood lipid levels. After assessing the relevant risks, it was deemed necessary to perform an emergency computed tomography (CT)-guided percutaneous drainage tube placement procedure targeting the necrotic area of the pancreas while the patient was still intubated. Finally, the patient was discharged from the hospital. Conclusion: The case highlights the association between fat overload syndrome and pancreatitis as well as the use of lipid emulsions and suggests the treatment strategies for severe fat overload syndrome.

Construction and application of NiCo2O4@MnS composite with hierarchical structure for hybrid supercapacitor.

The development of an electrochemical energy storage system with exceptional performance is an important way to address the energy crisis and environmental pollution of the modem world. In this study, an NiCo2O4@MnS composite with a unique hierarchical structure has been successfully synthesized on an NF substrate using the hydrothermal-electrodeposition method. The results indicate that NiCo2O4@MnS possesses superior specific capacitance and excellent cycling stability. At a current density of 2 A g-1, its specific capacitance can reach 2100 F g-1, while the capacitance retention is still 76% after 10 000 cycles at 10 A g-1. Moreover, when the current density is 1 A g-1, the assembled NiCo2O4@MnS//AC device can deliver a specific capacitance of 203 F g-1, and the energy density is up to 55 W h kg-1 at a power density of 697 W kg-1. These outstanding electrochemical properties of NiCo2O4@MnS can be ascribed to the increase in ion diffusion, specific surface area and electronic conductivity due to its unique hierarchical structure and introduction of MnS.

Exploring the topic structure and abuse trends of new psychoactive Substance since the 21st century from a bibliometric perspective.

Nowadays, NPS abuse are continuing to expand in terms of harm and scope, due to its cheap and easy to manufacture anywhere in the world. This study reviewed articles related to seven heavily abused NPS to analyze the structure and trends of NPS abuse. A total of 2476 articles were retrieved based on the search strategy for bibliometric analysis. A significant trend of research in recent years was the increasing number of research on synthetic opioids and designer benzodiazepines, but synthetic cannabinoid and synthetic cathinone still dominate, which were mainly concerned with the development of metabolic models and determining methods as well as their abuse characteristics and reasons. However, with the introduction of class-wide ban on synthetic cannabinoid in China and a series of enhancements in other countries, the abuse of it might decrease to some extent, but more than 20 kinds of synthetic cannabinoid beyond the scope of ban in China still reminded researchers of their potential threats. As for synthetic cathinone, an important phenomenon was some of the drugs first identified during certain period might be more widely distributed in the future. Besides, several problems such as the regulation and prevention mode of emerging NPS, development of testing technologies as well as the interpretation and identification of multiple NPS combinations were also worth paying attention to. This study could help entrants better understand the structure of NPS abuse and provided direction for future research in forensic toxicology.

Analysis on dynamic changes of etizolam and its metabolites and exploration of its development prospect using UPLC-Q-exactive-MS.

As one of the most widely abused designer benzodiazepines in the world, etizolam has been found in many cases in many countries. In this study, UPLC-Q-Exactive-MS was used for the first time to establish a dynamic change model of etizolam and its metabolites in rats. Compared with previous studies, the detection sensitivity and reproducibility of the instrument were higher. In the experiment, we optimized the traditional pharmacokinetic model based on Gauss function. According to the significant difference of etizolam in the plasma elimination phase of rats, a new pharmacokinetic model based on Lorentz function was established to describe the dynamic changes of etizolam more rigorously, which made the error effects lower and the accuracy of the pharmacokinetic parameters was improved. At the same time, the pharmacokinetic parameters of etizolam were compared with four other designer benzodiazepines reported in previous studies in rats, and we found the direct reason for the popularity of etizolam in the NPS market and explored the future development of etizolam for the first time. In addition, 21 metabolites were found through rat experiments to effectively detect etizolam abuse for a long time, of which 4 metabolites had the longest detection window and could be used as long-acting metabolites for experiments, which greatly prolongs the detection window and extends the time range in which etizolam was detected in real cases. This study is the first to conduct a systematic and comprehensive study on the metabolism and pharmacokinetics of etizolam and find out the direct reason for the prevalence of etizolam abuse, and we also discuss the development trend of etizolam in the future market of new psychoactive substances, which is beneficial for forensic experts to assess the trend of drug abuse and can provide reference for relevant drug control and drug treatment.

Mg doping of NiMn-LDH with a three-dimensional porous morphology for an efficient supercapacitor.

As a promising supercapacitor electrode material, NiMn-LDH has attracted great attention due to its high theoretical capacity and easy preparation. However, the development and application of NiMn-LDH in supercapacitors are limited because of its poor cycling stability and low electrical conductivity. To solve these problems, a NiMnMg-LDH with a three-dimensional porous morphology has been successfully fabricated by doping with Mg to improve its electrochemical properties. Experimental results indicate that NiMnMg-LDH-7 delivers a specific capacitance of 1772 F g-1 at a current density of 1 A g-1. Moreover, it can still reach 1080 F g-1 when the current density is increased 10 times, suggesting excellent rate capability. The asymmetric supercapacitor (ASC) NiMnMg-LDH-7//AC can provide a high energy density of 28 W h kg-1 at a power density of 700 W kg-1. Furthermore, the energy density can still reach 16 W h kg-1 even if the power density is increased to close to 3500 W kg-1. The capacity retention of this ASC device can reach 74% after 3000 cycles at a current density of 3 A g-1. These excellent properties of NiMnMg-LDH can be attributed to the obvious improvement of its specific surface area and electrical conductivity owing to doping with the element magnesium. We believe that this work could provide a new idea for the preparation of high-performance electrode materials for supercapacitors.

Metabolic Profile Analysis of Designer Benzodiazepine Etizolam in Zebrafish and Human Liver Microsomes.

As one of the most widely abused designer benzodiazepines worldwide, Etizolam is characterized by its high addiction potential, low production cost, and difficulty in detection. Due to the rapid metabolism of Etizolam in the human body, the probability of detecting the Etizolam parent drug in actual case samples by forensic personnel is low. Therefore, without detecting the parent drug, analysis of Etizolam metabolites can help forensic personnel provide references and suggestions on whether the suspect has taken Etizolam. This study simulates the objective metabolic process of the human body. It establishes a zebrafish in vivo metabolism model and a human liver microsome in vitro metabolism model to analyze the metabolic characteristics of Etizolam. A total of 28 metabolites were detected in the experiment, including 13 produced in zebrafish, 28 produced in zebrafish urine and feces, and 17 produced in human liver microsomes. The UPLC-Q-Exactive-MS technology was used to analyze the structures and related metabolic pathways of Etizolam metabolites in zebrafish and human liver microsomes, and a total of 9 metabolic pathways were identified, including monohydroxylation, dihydroxylation, hydration, desaturation, methylation, oxidative deamination to alcohol, oxidation, reduction acetylation, and glucuronidation. Among them, metabolites involving hydroxylation reactions (including monohydroxylation and dihydroxylation) accounted for 57.1% of the total number of potential metabolites, indicating that hydroxylation may be the major metabolic pathway of Etizolam. Based on the response values of each metabolite, monohydroxylation (M1), desaturation (M19), and hydration (M16) were recommended as potential biomarkers for Etizolam metabolism. The experimental results provide reference and guidance for forensic personnel in identifying Etizolam use in suspects.

Advances in detecting fruit aroma compounds by combining chromatography and spectrometry.

Fruit aroma is produced by volatile compounds, which can significantly enhance fruit flavor. These compounds are highly complex and have remarkable pharmacological effects. The synthesis, concentration, type, and quantity of fruit aroma substances are affected by various factors, both abiotic and biotic. To fully understand the aroma substances of various fruits and their influencing factors, detection technology can be used. Many methods exist for detecting aroma compounds, and approaches combining multiple instruments are widely used. This review describes and compares each detection technology and discusses the potential use of combined technologies to provide a comprehensive understanding of fruit aroma compounds and the factors influencing their synthesis. These results can inform the development and utilization of fruit aroma substances. © 2023 Society of Chemical Industry.

Identification, characterization, and expression profiling of the putative U-box E3 ubiquitin ligase gene family in Sorghum bicolor.

The U-box family is one of the main E3 ubiquitin ligase families in plants. The U-box family has been characterized in several species. However, genome-wide gene identification and expression profiling of the U-box family in response to abiotic stress in Sorghum bicolor remain unclear. In this study, we broadly identified 68 U-box genes in the sorghum genome, including 2 CHIP genes, and 1 typical UFD2 (Ub fusion degradation 2) gene. The U-box gene family was divided into eight subclasses based on homology and conserved domain characteristics. Evolutionary analysis identified 14, 66, and 82 U-box collinear gene pairs in sorghum compared with arabidopsis, rice, and maize, respectively, and a unique tandem repeat pair (SbPUB26/SbPUB27) is present in the sorghum genome. Gene Ontology (GO) enrichment analysis showed that U-box proteins were mainly related to ubiquitination and modification, and various stress responses. Comprehensive analysis of promoters, expression profiling, and gene co-regulation networks also revealed that many sorghum U-box genes may be correlated with multiple stress responses. In summary, our results showed that sorghum contains 68 U-box genes, which may be involved in multiple abiotic stress responses. The findings will support future gene functional studies related to ubiquitination in sorghum.

Plant protein-coding gene families: Their origin and evolution.

Steady advances in genome sequencing methods have provided valuable insights into the evolutionary processes of several gene families in plants. At the core of plant biodiversity is an extensive genetic diversity with functional divergence and expansion of genes across gene families, representing unique phenomena. The evolution of gene families underpins the evolutionary history and development of plants and is the subject of this review. We discuss the implications of the molecular evolution of gene families in plants, as well as the potential contributions, challenges, and strategies associated with investigating phenotypic alterations to explain the origin of plants and their tolerance to environmental stresses.

Transcriptomics-based analysis of genes related to lead stress and their expression in the roots of Pogonatherum crinitum.

Revealing plants' tolerance and transport genes to heavy metal stress play an important role in exploring the potential of phytoremediation. Taking the heavy metal lead (Pb) hyperaccumulator plant Pogonatherum crinitum (Thunb.) Kunth as the research object, a hydroponic simulation stress experiment was set up to determine the physiological indicators such as antioxidant enzymes and non-enzymatic antioxidants in the roots of P. crinitum under different Pb concentrations (0, 300, 500, 1000, 2000 mg·L-1). RNA-Seq was performed, the Unigenes obtained by transcriptome sequencing were enriched and annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, and the differential expression genes (DEGs) of root were screened and verified by quantitative real-time polymerase chain reaction (qRT-PCR). The results are as follows: with the increase of Pb concentration, superoxide dismutase (SOD), catalase (CAT), and ascorbic acid (AsA) content increased. Peroxidase (POD), malondialdehyde (MDA), and ascorbic acid-glutathione (AsA-GSH) cycles showed low promotion with high inhibition. A total of 38.21 Gb of bases were obtained by transcriptome sequencing, and the base quality of each sample reached Q20 and Q30, accounting for 90%, making the sequencing results reliable. Combined with transcriptome sequencing, functional annotation, and qRT-PCR validation results, 17 root Pb-tolerant genes of P. crinitum were screened out, which were related to antioxidation, transportation, and transcription functions. Moreover, qRT-PCR verification results under different Pb stress concentrations were consistent with the transcriptome sequencing results and changes in physiological indicators. In brief, the root of P. crinitum can adapt to the Pb stress environment by up-regulating the expression of related genes to regulate the physiological characteristics.

Lead contamination alters enzyme activities and microbial composition in the rhizosphere soil of the hyperaccumulator Pogonatherum crinitum.

Pogonatherum crinitum is a promising lead (Pb) hyperaccumulator; however, the effects of Pb contamination on P. crinitum rhizosphere soil enzymatic activities and microbial composition remain largely unexplored. Thus, an indoor experiment was conducted by cultivating P. crinitum seedlings and exposing them to four Pb concentrations (0, 1,000, 2000 and 3000 mg/kg Pb). Protease, urease, acid phosphatase and invertase activities were determined using standard methods while soil bacterial composition was determined by 16 S rDNA sequencing. The results showed that rhizosphere soil acid phosphatase activity significantly increased with increasing Pb concentration, while urease activity was significantly greater in rhizosphere soil contaminated with 1000 and 2000 mg/kg than in the control. There was a clear shift in bacterial composition during phytoremediation by P. crinitum. Compared to the control, Bacteroidetes was more abundant in all Pb-contaminated soils, Actinobacteria was more abundant in 1000 mg/kg Pb-treated soil, and Firmicutes was more abundant in 3000 mg/kg Pb-treated soil. Positive correlations were observed between dominant bacterial phyla and soil enzyme activities. Metabolic pathways, such as ABC transporter, quinine reductase, and ATP-binding protein were significantly increased in rhizosphere soil bacteria with Pb contamination. In conclusion, Pb contamination differentially influenced the activities of rhizosphere soil enzymes, specifically increasing acid phosphatase and urease activities, and alters the dominance of soil bacteria through up-regulation of genes related to some metabolic pathways. The strong correlations between dominant bacterial phyla and enzymatic activities suggest synergetic effects on the growth of P. crinitum during Pb contamination.

Strength and size of phosphorus-rich patches determine the foraging strategy of Neyraudia reynaudiana.

BACKGROUND: Under natural conditions, soil nutrients are heterogeneously distributed, and plants have developed adaptation strategies to efficiently forage patchily distributed nutrient. Most previous studies examined either patch strength or patch size separately and focused mainly on root morphological plasticity (increased root proliferation in nutrient-rich patch), thus the effects of both patch strength and size on morphological and physiological plasticity are not well understood. In this study, we examined the foraging strategy of Neyraudia reynaudiana (Kunth) Keng ex Hithc, a pioneer grass colonizing degraded sites, with respect to patch strength and size in heterogeneously distributed phosphorus (P), and how foraging patchily distributed P affects total plant biomass production. Plants were grown in sand-culture pots divided into ½, », 1/6 compartments and full size and supplied with 0 + 0/30, 0 + 7.5/30 and 7.5 + 0/30 mg P/kg dry soil as KH2PO4 or 0 + 15/15, 0 + 18.5/ 18.5, 7.5 + 15/15 mg kg - 1 in the homogenous treatment. The first amount was the P concentration in the central region, and that the second amount was the P concentration in the outer parts of the pot. RESULTS: After 3 months of growth under experimental conditions, significantly (p < 0.05) high root elongation, root surface area, root volume and average root diameter was observed in large patches with high patch strength. Roots absorbed significantly more P in P-replete than P-deficient patches. Whole plant biomass production was significantly higher in larger patches with high patch strength than small patches and homogeneous P distribution. CONCLUSION: The result demonstrates that root morphological and physiological plasticity are important adaptive strategies for foraging patchily distributed P and the former is largely determined by patch strength and size. The results also establish that foraging patchily distributed P resulted in increased total plant biomass production compared to homogeneous P distribution.

Single-Crystal MoO3 Micrometer and Millimeter Belts Prepared from Discarded Molybdenum Disilicide Heating Elements.

Single-crystal MoO3 micrometer to millimeter even centimeter belts were prepared via a novel route of oxidizing a discarded molybdenum disilicide heating element at 1000 °C for 3 h. The morphology and structure features, and growth mechanism of the products were evidently investigated by X-ray diffraction, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy, and transmission electron microscopy. The results indicated that the powdery and fibrous products were typical α-MoO3 belt-like structures which size could develop from micrometer to several millimeter even centimeter in length and up to 0.5 mm in width. It should be formed preferentially along the [001] direction via layer by layer growth to form 1-D single MoO3 belts by vapor-solid mechanism. Thermal and luminescence properties of the products were revealed by thermogravimetric analysis and differential thermal analysis and photoluminescence spectra that the resultant α-MoO3 belts had good thermal stability and characteristics of luminescence with a central peak at 481 nm. The MoO3 belts are of good potential being applied to luminescent and high temperature devices.

(2R,3R)Dihydromyricetin inhibits osteoclastogenesis and bone loss through scavenging LPS-induced oxidative stress and NF-κB and MAPKs pathways activating.

Osteolysis is a serious complication of several chronic inflammatory diseases and is closely associated with a local chronic inflammatory reaction with a variety of causes. However, similarities exist in the mechanisms of their pathological processes. Inflammatory factors and oxidative stress-induced nuclear factor κB (NF-κB) and mitogen-activated protein kinases (MAPKs) signaling pathways play a center role in bone erosion. Dihydromyricetin (DMY) is a natural compound with anti-inflammatory and antioxidative effect, which are commonly used in chronic pharyngitis and alcohol use disorders. In the current study, we identified that DMY attenuated lipopolysaccharide (LPS)-induced oxidative stress through inhibiting the production of reactive oxygen species (ROS) and nitric oxide (NO), downregulated COX-2 and iNOS, and promoted the activity of the antioxidative system by activating superoxide dismutase (SOD) and Nrf2/HO-1 pathway. To further investigate the underlying mechanism, we found that DMY inhibits osteoclast (OC) differentiation and bone resorption activity through blocking the RANKL-induced activation of the NF-κB and MAPKs signaling pathways and then downregulated c-Fos and NFATc1, which is essential for OC differentiation. Furthermore, DMY inhibited LPS-induced osteolysis in vivo. Collectively, these results indicate that DMY might be a promising prophylactic antiosteoclastic/resorptive agent in preventing or treating bone lysis diseases.

Uptake and Transport Mechanism of Dihydromyricetin Across Human Intestinal Caco-2 Cells.

A variety of beneficial pharmacological activities have been reported for dihydromyricetin (DMY), however, its oral bioavailability is poor and the intestinal absorption profiles of DMY remains unknown. The aim of this study was to investigate the uptake and transport mechanism of DMY in human intestinal Caco-2 cells. DMY was detected using a liquid chromatography-tandem mass spectrometry method. Several factors including time, concentration, pH, temperature and efflux transporters were systematically evaluated. DMY was poorly absorbed by a passive diffusion mechanism. The uptake and transport of DMY were time and concentration dependent. Interestingly, decreasing the pH from 8.0 to 6.0 markedly enhanced the DMY uptake, but didn't significantly affect its bidirectional transport. Efflux transporters, multidrug resistance protein 2 and breast cancer resistance protein also influenced the DMY uptake and transport processes. This work details the uptake and transport characteristics of DMY and provides basis for future study. PRACTICAL APPLICATION: This study elucidated the uptake and transport characteristics of dihydromyricetin (DMY). DMY was poorly absorbed by a passive diffusion mechanism. The uptake and transport of DMY were time and concentration dependent. Interestingly, pH affected DMY uptake but not its bidirectional transport. MRP2 and BCRP were involved in the uptake and transport of DMY, which hindered the absorption of DMY in the intestinal. Thus, the present study may provide useful information for designing DMY delivery systems and avoiding DMY-drug interactions.

Tissue Distribution, Excretion, and Metabolic Profile of Dihydromyricetin, a Flavonoid from Vine Tea (Ampelopsis grossedentata) after Oral Administration in Rats.

Dihydromyricetin (DMY), a flavanonol compound found as the most abundant and bioactive constituent in vine tea (Ampelopsis grossedentata), possesses numerous biological activities. In the present study, an HPLC-MS/MS method for the determination of DMY in tissues, urine, and feces was developed and applied to the tissue distribution and excretion study after oral administration in rats, and the metabolic profile of DMY was further investigated using UPLC-QTOF-MS. The results indicated that DMY could be distributed rapidly in various tissues and highly in the gastrointestinal tract. The elimination of DMY occurred rapidly as well, and most unconverted forms were excreted in feces. A total of eight metabolites were identified in urine and feces, while metabolites were barely found in plasma. The predicted metabolic pathways including reduction, dehydroxylation, methylation, glucuronidation, and sulfation were proposed. The present findings may provide the theoretical basis for evaluating the biological activities of DMY and will be helpful for its future development and application.

Shear Stress-sensitive Carriers for Localized Drug Delivery.

Stenosis of the critical blood vessels, which occurs in a variety of cardiovascular and cerebrovascular diseases, is one of leading causes of death in the world. Vascular stenosis will significantly alter the hemodynamic features in the vessel. Hemodynamic shear stress, one of the most important physical parameters of blood flow, will be dramatically elevated at the stenotic site. When platelets flow through the constricted site, they will sense these abnormally high shear stresses, and then respond by activating, sticking to the vascular wall, and aggregating at these sites. The shear-dependent platelet activation inspired a novel targeting platform-shear stress activated drug targeting delivery. The shear-activated drug delivery systems preferentially release their content under elevated shear stress, providing a novel approach to cure various diseases, in particular, cardiovascular diseases. In this review, we, on one hand, introduced the features of hemodynamic shear stress under both physiological and pathological conditions. On the other hand, we summarized the carriers displaying sensitivity to shear stress, such as liposomes, aggregations, gels, emulsions, in addition to the factors affecting the mechanical properties of them. Lastly, the clinical applications and prospects of this novel drug targeting strategy were discussed. It is hoped that, with a better understanding of shear stress-sensitive carriers and their targeted principle, a novel targeted drug delivery strategy will be one day applied in the clinics of the future.

Lead tolerance mechanism in Conyza canadensis: subcellular distribution, ultrastructure, antioxidative defense system, and phytochelatins.

We used hydroponic experiments to examine the effects of different concentrations of lead (Pb) on the performance of the Pb-tolerable plant Conyza canadensis. In these experiments, most of the Pb was accumulated in the roots; there was very little Pb accumulated in stems and leaves. C. canadensis is able to take up significant amounts of Pb whilst greatly restricting its transportation to specific parts of the aboveground biomass. High Pb concentrations inhibited plant growth, increased membrane permeability, elevated antioxidant enzyme activity in roots, and caused a significant increase in root H2O2 and malondialdehyde content. Analysis of Pb content at the subcellular level showed that most Pb was associated with the cell wall fraction, followed by the nucleus-rich fraction, and with a minority present in the mitochondrial and soluble fractions. Furthermore, transmission electron microscopy and energy dispersive X-ray analysis of root cells revealed that the cell wall and intercellular space in C. canadensis roots are the main locations of Pb accumulation. Additionally, high Pb concentrations adversely affected the cellular structure of C. canadensis roots. The increased enzyme activity suggests that the antioxidant system may play an important role in eliminating or alleviating Pb toxicity in C. canadensis roots. However, the levels of non-protein sulfhydryl compounds, glutathione, and phytochelatin did not significantly change in either the roots or leaves under Pb-contaminated treatments. Our results provide strong evidence that cell walls restrict Pb uptake into the root and act as an important barrier protecting root cells, while demonstrating that antioxidant enzyme levels are correlated with Pb exposure. These findings demonstrate the roles played by these detoxification mechanisms in supporting Pb tolerance in C. canadensis.

Determination of dihydromyricetin in rat plasma by LC-MS/MS and its application to a pharmacokinetic study.

Ampelopsis grossedentata (Hand.-Mazz.) W.T. Wang has long been used as a traditional Chinese medicinal herb among the indigenous people in the Yangtze River region of China. Dihydromyricetin (DMY) is the most abundant (approximately 30%) and bioactive constituent in A. grossedentata (Hand.-Mazz.) W.T. Wang, and recent studies have demonstrated its various pharmacological activities. In the present study, a first specific, sensitive, rapid and reliable LC-MS/MS method for the determination of DMY in rat plasma was developed and validated. The plasma samples were prepared with protein precipitation method, and chromatographic separation was performed on a Welch Ultimate XB-C18 column (50 × 2.1 mm, 5 µm) using a gradient elution with water and acetonitrile. The mass spectrometry (MS) analysis was conducted in negative ionization mode with multiple reaction monitoring (MRM) transitions at m/z 319.1→192.8 for DMY and m/z 609.0→301.2 for rutin (IS). The plasma concentration profiles and pharmacokinetic parameters were analyzed after oral administration of dextroisomer and racemate DMY at the dose of 100 mg/kg in rats. The method validation was conducted over the calibration range of 10.0-5000 ng/ml with the intra- and inter-day precision and accuracy within 12.0% (RSD) and 5.6% (RE). The recoveries, matrix effect and stability under different conditions were all proved acceptable. The values of Tmax, AUC(0-∞) and Vd were significantly different between the groups of dextroisomer and racemate DMY (P<0.05), and pharmacokinetic results revealed their poor absorptions into blood, probably high tissue distributions and slow elimination processes. The present study will provide helpful information for the further studies and future clinical applications of DMY.

Dihydromyricetin protects endothelial cells from hydrogen peroxide-induced oxidative stress damage by regulating mitochondrial pathways.

HEADING AIMS: Dihydromyricetin (DMY) is the most abundant ingredient in vine tea. Here, we investigated the cytoprotective effects and possible mechanisms of DMY on hydrogen peroxide (H2O2)-induced oxidative stress damage in human umbilical vein endothelial cells (HUVECs). MATERIALS AND METHODS: The percentage of cell viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. We determined the antioxidant properties of DMY by measuring the activity of superoxide dismutase (SOD) and malondialdehyde (MDA). Flow cytometry was used to measure apoptosis in HUVECs that were double stained with Hoechst 33342 and propidium iodide (PI). The generation of intracellular reactive oxygen species (ROS) was measured in 2',7'-dichlorofluorescin diacetate (DCFH-DA)-loaded HUVECs using a fluorescent microscope. Moreover, the expression of apoptosis-related proteins was determined by Western blotting. In addition, the release of nitric oxide (NO) was analyzed using a commercial kit. KEY FINDINGS: HUVECs treated with H2O2 had a notable decrease in cell viability that was attenuated when cells were pretreated with DMY (37.5-300µM). DMY pretreatment significantly attenuated H2O2-induced apoptosis in HUVECs and inhibited intracellular ROS overproduction. Finally, pretreatment of cells with DMY prior to H2O2 exposure resulted in the inhibition of p53 activation, followed by the regulation of the expression of Bcl-2 and Bax, the release of cytochrome c, the cleavage (activation) of caspase-9 and caspase-3, and then the suppression of PARP cleavage in H2O2-induced HUVECs. SIGNIFICANCE: Our study is the first to report that DMY can protect HUVECs from oxidative stress damage, an effect that is mediated by the mitochondrial apoptotic pathways.