A Novel Homozygous Mutation Causing Complete TYK2 Deficiency, with Severe Respiratory Viral Infections, EBV-Driven Lymphoma, and Jamestown Canyon Viral Encephalitis.

Autosomal recessive tyrosine kinase 2 (TYK2) deficiency is characterized by susceptibility to mycobacterial and viral infections. Here, we report a 4-year-old female with severe respiratory viral infections, EBV-driven Burkitt-like lymphoma, and infection with the neurotropic Jamestown Canyon virus. A novel, homozygous c.745C > T (p.R249*) variant was found in TYK2. The deleterious effects of the TYK2 lesion were confirmed by immunoblotting; by evaluating functional responses to IFN-α/ß, IL-10, and IL-23; and by assessing its scaffolding effect on the cell surface expression of cytokine receptor subunits. The effects of the mutation could not be pharmacologically circumvented in vitro, suggesting that alternative modalities, such as hematopoietic stem cell transplantation or gene therapy, may be needed. We characterize the first patient from Canada with a novel homozygous mutation in TYK2.

Elucidation of the Mechanisms and Molecular Targets of Run-zao-zhiyang Capsule for Itch based on Network Pharmacology, Molecular Docking and In Vitro Experiment.

BACKGROUND: Traditional Chinese medicine formula (TCMF) Run-zao-zhi-yang capsule (RZZY) is commonly used in treating itch in China. However, there are few studies on its mechanisms. In this study, we revealed the mechanisms and molecular targets of RZZY for itch by network pharmacology, molecular docking, and in vitro experiments. METHODS: The network pharmacology consisted of active ingredient collection, target acquisition, enrichment analysis, biological process analysis, and network construction. Molecular docking was carried out using molegro virtual docker (MVD) software. LPS-induced RAW 264.7 cells were used to evaluate the in vitro anti-inflammatory activity. RESULTS: We collected 483 high-confidence targets that interacted with 16 active compounds of RZZY, including 121 common genes related to itch. 43 important targets and 20 important pathways were identified according to the network and system analysis. Target-pathway network function analysis suggested that RZZY is treated for itch by multiple ways in immune regulation, hormone adjustment, anti-inflammation, and anti-oxidation. Molecular docking results demonstrated that daidzein and formononetin could be closely combined with 4 proteins. In vitro experiments displayed that RZZY, sophocarpine, catalpol, emodin, and daidzein had suppressive effects against TNF-α, IL-1ß, or IL-6 production in LPS-induced RAW 264.7 cells. Interestingly, the result of network pharmacology revealed that RZZY might be more suitable for senile pruritus, consistent with the bibliometric analysis of RZZY's clinical indications. CONCLUSION: This study illustrated the potential mechanisms and molecular targets of RZZY for itch, which may contribute to the proper use of RZZY in clinical practice.

The degradation of municipal solid waste incineration leachate by UV/persulfate and UV/H2O2 processes: The different selectivity of SO4•- and •OH.

In this work, the different selectivity of SO4•- and •OH towards municipal solid waste incineration leachates (MSWILs) was studied by a comparative study of UV/persulfate (PS) and UV/H2O2. Results showed SO4•- preferentially mineralized carbon atoms of higher average oxidation state, while •OH showed a two-stage mechanism of partial oxidation and mineralization successively. Electron spin resonance (ESR) analysis showed SO4•- had superior selectivity towards MSWILs than •OH, and Fe(II) would significantly affect the selectivity via forming Fe-MSWILs complex. As the consequence, Fe(II) showed slightly negative effect on UV/PS, but greatly enhanced the performance of UV/H2O2/Fe(II). High concentration of Cl- affected the degradation of non-fluorescent substances by UV/PS, while SO42- and NO3- showed no effect. In contrast, anions showed no effect on UV/H2O2. In addition, •OH preferentially attacked large molecules, but SO4•- showed no selectivity. This study further revealed the selectivity of SO4•- and •OH in the treatment of hypersaline wastewater, and provided theoretical support for the development of targeted technology.

Moyamoya syndrome with ruptured aneurysm in α-thalassemia: A case report.

Moyamoya syndrome (MMS) refers to the moyamoya vascular disease associated with various systemic diseases and conditions, including sickle cell anemia, Fanconi anemia and iron deficiency anemia. However, the association between MMS and other hemoglobinopathies is less frequently observed. MMS, like moyamoya disease, is a cerebrovascular condition that is characterized by chronic progressive stenosis or occlusion at the ends of the bilateral internal carotid arteries, anterior cerebral arteries and the beginning of the middle cerebral arteries, and is secondary to the formation of an abnormal vascular network at the base of the skull. Patients with MMS are prone to thrombosis, aneurysm and bleeding. The present study reports the case of a 43-year-old man with α-thalassemia who presented with moyamoya vessels with a ruptured aneurysm bleeding into the ventricle. α-thalassemia is considered as an extremely rare but potential cause of MMS. Since MMS is a progressive disease, early diagnosis and treatment is vital to prevent the disease from worsening.

Preparation and Characterization of Calcium-Incorporated Rosa roxburghii Tratt and Its Efficacy on Bone Mineral Density in Rats.

The deficiency of traditional calcium preparation will gradually be replaced by the new type of calcium preparation. Rosa roxburghii fruit (R. roxburghii) is popular for its rich nutrients and functional ingredients. The fermentation broth of R. roxburghii, involving amino acids, flavonoids, triterpenes, polysaccharides, and other compounds, is favorable for calcium chelation. Thus, this study fabricated calcium-incorporated R. roxburghii (FECa) and further illustrated its efficacy on bone mineral density (BMD) in rats. The calcium holding capacity of FECa was identified and confirmed using AAS. Ion complexation of FECa was characterized using 1H-NMR, UV, SEM and EDS, and FTIR. The calcium contents of femurs were increased by 36%, and the bone trabeculae of femurs were significantly increased. Net calcium balance was enhanced to further improve BMD by oral administration of FECa. The above results indicate that FECa can be a potential and efficient calcium supplementation agent.

Real-world serological responses to extended-interval and heterologous COVID-19 mRNA vaccination in frail, older people (UNCoVER): an interim report from a prospective observational cohort study.

BACKGROUND: The use of COVID-19 vaccines has been prioritised to protect the most vulnerable-notably, older people. Because of fluctuations in vaccine availability, strategies such as delayed second dose and heterologous prime-boost have been used. However, the effectiveness of these strategies in frail, older people are unknown. We aimed to assess the antigenicity of mRNA-based COVID-19 vaccines in frail, older people in a real-world setting, with a rationed interval dosing of 16 weeks between the prime and boost doses. METHODS: This prospective observational cohort study was done across 12 long-term care facilities of the Montréal Centre-Sud - Integrated University Health and Social Services Centre in Montréal, Québec, Canada. Under a rationing strategy mandated by the provincial government, adults aged 65 years and older residing in long-term care facilities in Québec, Canada, with or without previously documented SARS-CoV-2 infection, were administered homologous or heterologous mRNA vaccines, with an extended 16-week interval between doses. All older residents in participating long-term care facilities who received two vaccine doses were eligible for inclusion in this study. Participants were enrolled from Dec 31, 2020, to Feb 16, 2021, and data were collected up to June 9, 2021. Clinical data and blood samples were serially collected from participants at the following timepoints: at baseline, before the first dose; 4 weeks after the first dose; 6-10 weeks after the first dose; 16 weeks after the first dose, up to 2 days before administration of the second dose; and 4 weeks after the second dose. Sera were tested for SARS-CoV-2-specific IgG antibodies (to the trimeric spike protein, the receptor-binding domain [RBD] of the spike protein, and the nucleocapsid protein) by automated chemiluminescent ELISA. Two cohorts were used in this study: a discovery cohort, for which blood samples were collected before administration of the first vaccine dose and longitudinally thereafter; and a confirmatory cohort, for which blood samples were only collected from 4 weeks after the prime dose. Analyses were done in the discovery cohort, with validation in the confirmatory cohort, when applicable. FINDINGS: The total study sample consisted of 185 participants. 65 participants received two doses of mRNA-1273 (Spikevax; Moderna), 36 received two doses of BNT162b2 (Comirnaty; Pfizer-BioNTech), and 84 received mRNA-1273 followed by BNT162b2. In the discovery cohort, after a significant increase in anti-RBD and anti-spike IgG concentrations 4 weeks after the prime dose (from 4·86 log binding antibody units [BAU]/mL to 8·53 log BAU/mL for anti-RBD IgG and from 5·21 log BAU/mL to 8·05 log BAU/mL for anti-spike IgG), there was a significant decline in anti-RBD and anti-spike IgG concentrations until the boost dose (7·10 log BAU/mL for anti-RBD IgG and 7·60 log BAU/mL for anti-spike IgG), followed by an increase 4 weeks later for both vaccines (9·58 log BAU/mL for anti-RBD IgG and 9·23 log BAU/mL for anti-spike IgG). SARS-CoV-2-naive individuals showed lower antibody responses than previously infected individuals at all timepoints tested up to 16 weeks after the prime dose, but achieved similar antibody responses to previously infected participants by 4 weeks after the second dose. Individuals primed with the BNT162b2 vaccine showed a larger decrease in mean anti-RBD and anti-spike IgG concentrations with a 16-week interval between doses (from 8·12 log BAU/mL to 4·25 log BAU/mL for anti-RBD IgG responses and from 8·18 log BAU/mL to 6·66 log BAU/mL for anti-spike IgG responses) than did those who received the mRNA-1273 vaccine (two doses of mRNA-1273: from 8·06 log BAU/mL to 7·49 log BAU/mL for anti-RBD IgG responses and from 6·82 log BAU/mL to 7·56 log BAU/mL for anti-spike IgG responses; mRNA-1273 followed by BNT162b2: from 8·83 log BAU/mL to 7·95 log BAU/mL for anti-RBD IgG responses and from 8·50 log BAU/mL to 7·97 log BAU/mL for anti-spike IgG responses). No differences in antibody responses 4 weeks after the second dose were noted between the two vaccines, in either homologous or heterologous combinations. INTERPRETATION: Interim results of this ongoing longitudinal study show that among frail, older people, previous SARS-CoV-2 infection and the type of mRNA vaccine influenced antibody responses when used with a 16-week interval between doses. In these cohorts of frail, older individuals with a similar age and comorbidity distribution, we found that serological responses were similar and clinically equivalent between the discovery and confirmatory cohorts. Homologous and heterologous use of mRNA vaccines was not associated with significant differences in antibody responses 4 weeks following the second dose, supporting their interchangeability. FUNDING: Public Health Agency of Canada, Vaccine Surveillance Reference Group; and the COVID-19 Immunity Task Force. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Proteomics and bioinformatics analysis of Fasciola hepatica somatic proteome in different growth phases.

Fasciola hepatica (F. hepatica) is a well-known zoonotic parasite that is crucial for economic and public health worldwide. Quantitative proteomics studies have been performed on proteins expressed by F. hepatica to investigate the differential expression of proteomes in different growth phases. And the screening of several marker proteins for use as early diagnostic antigens is essential. In this study, high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) was conducted to analyze the differences in the expression of F. hepatica somatic proteins in different growth phases. Furthermore, gene ontology (GO) functional annotation, KEGG metabolic pathway, and clustering analyses were also performed. LC-MS/MS identified 629, 2286, 2254, and 2192 proteins in metacercariae, juvenile flukes 28dpi, immature flukes 59dpi, and adult phases, respectively. GO analysis revealed that differentially expressed proteins (DEPs) were mainly involved in transport, localization, metabolism, enzyme regulation, protein folding and binding, and nucleoside and nucleotide binding. The DEPs were enriched in cells, intracellular components, organelles, cytoplasm, vesicles, and membranes. KEGG pathway annotation results showed that the DEPs were involved in metabolism, genetic information processing, environmental information processing, cellular processes, organismal systems, and other processes. These findings provide a theoretical basis for vaccine development and establishing early diagnostic methods in the future.

[Treatment efficacy of Solitaire stent- and LVIS stent-assisted coil embolization for intracranial wide-neck carotid aneurysm].

OBJECTIVE: To compare the safety, efficacy and complications of LVIS stent-assisted coil embolization and Solitaire stent-assisted coil embolization for management of intracranial wide-neck carotid aneurysms. METHODS: We retrospectively analyzed the data of 86 patients with intracranial wide-neck carotid aneurysm treated in our hospital between June, 2016 and June, 2019. Forty-three of the patients received LVIS stent-assisted coil tamponade and the other 43 received Solitaire stentassisted coil tamponade. Arteriography was performed during, immediately after, and at 3 months after the surgery. The immediate embolization rate, surgical complications (vascular spasm, acute thrombus, coil escape, and bleeding), and the recurrence rate were compared between the two groups. RESULTS: In the LVIS stent group, 37 aneurysms were completely embolized, 5 were nearly fully embolized, and 1 was partially embolized, as compared with the numbers of 35, 6, and 2 in the Solitaire stent group, respectively. Surgery-related complications occurred in 5 patients in LVIS stent group and 3 in Solitaire stent group. Follow-up digital subtraction angiography (DSA) at 3 months after the operation revealed 4 recurrent aneurysms, including 1 in LVIS group and 3 in Solitaire stent group. All the patients had favorable outcomes that did not differ significantly between the two groups. CONCLUSIONS: Stent-assisted spring coils can achieve a high rate of complete and near-total embolization for intracranial aneurysms and is associated with a low incidence of neurological complications and favorable prognosis of the patients. The embolization rate, complications and recurrence rate are comparable between LVIS stent and Solitaire stent.

Effect of T. spiralis Serine protease inhibitors on TNBS-induced experimental colitis mediated by Macrophages.

Inflammatory bowel disease (IBD) is an autoimmune disease with increasing incidence rate, and divided into ulcerative colitis (UC) and Crohn's disease (CD). And more and more experimental evidence supports that immune disorder is important in the pathogenesis of IBD. Our previous experiments have confirmed that TsKaSPI and TsAdSPI recombinant proteins could relieve TNBS (2,4,6-Trinitrobenzenesulfonic acid solution)-induced colitis. Therefore, we speculate that macrophages play a certain role in the process of recombinant protein relieving colitis. In this experiment, 96 male BALB/c mice aged 6-8 weeks were randomly divided into two groups: the prevention group and the therapy group. Changes of the ratio of M1/M2 phenotypic macrophages in spleens and MLNs, key factors in the IL-33/ST2 and IL-6/JAK2/STAT3 signaling pathway were detected. The purpose is to analyze the specific role played by macrophages and their secreted cytokines in the immunomodulation of colitis by Trichinella spiralis (T. spiralis) Serine protease inhibitors. The results showed that the percentage of M1 phenotypic macrophages was decreased and M2 phenotypic macrophages was increased in the TsKaSPI + TNBS, TsAdSPI + TNBS group compared with the PBS + TNBS group in the prevention group. Meanwhile, the expression of IL-33 and ST2 were significantly decreased. The key factors of IL-6/JAK2/STAT3 signaling pathway were all significantly increased. In addition, in the therapy group, we found similar results. This experiment demonstrated that macrophages have a certain impact during this process of recombinant protein relieving mouse CD model.

Discrimination of Salvia miltiorrhiza Bunge from Different Geographical Locations Employing High-Performance Liquid Chromatography, Near-Infrared Fingerprinting Combined with Chemometrics.

To evaluate the quality of Salvia miltiorrhiza Bunge, high-performance liquid chromatography-diode array detector (HPLC/UV-PAD), near infrared (NIR) spectroscopy, and chemometrics were used to discriminate nine components of samples from four different geographical locations. HPLC was performed with a C18 (5 µm, 4.6 mm × 250 mm) column and 0.1% formic acid aqueous solution-acetonitrile with a gradient elution system. Orthogonal partial least squares discriminant analysis was used to identify the amounts of salvianolic acid B. NIR was used to distinguish rapidly S. miltiorrhiza Bunge samples from different geographical locations. In this assay, discriminant analysis was performed, and the accuracy was found to be 100%. The combination of these two methods can be used to quickly and accurately identify S. miltiorrhiza Bunge from different geographical locations.

Evaluation of a Community-Run and General-Practitioner-Supervised Self-Care for Minor Illnesses (CGPSC) Program in a Remote Area in Taiwan.

Although Taiwanese citizens benefit from affordable health care, residents in remote areas extensively rely on unsafe self-care practices because of a lack of easy access to medical services. To improve self-care safety, ten easy-access self-care medical spots (ESCMSs) managed by trained residents were established in two remote villages. This study aimed to assess the impact of ESCMSs on self-care and access to medical services. For a total of six commonly experienced minor illnesses, the average number of illnesses for which residents were confident to perform self-care increased from 2.78 in the pretest to 3.58 in the post-test. ESCMSs were also the first choice when experiencing minor illnesses for 31.25% residents who did not visit a doctor. Residents' personal experience with ESCMSs correlated with their perception of ESCMSs' function. Compared with residents who had no personal experience of using ESCMSs, those who used the ESCMS service were less likely to store medications for minor illnesses at home (51.02% vs. 76.67%). Furthermore, those who attribute the reduced needs for professional help to ESCMSs had used medications for minor illnesses at ESCMSs. These results suggest that establishing ESCMSs is a viable alternative to increase the self-care capacity of residents in remote areas and increase the access to medical resources. Moreover, because residents are less likely to store medication and travel for professional help, ESCMSs could indirectly reduce the risks of self-medication and traffic accidents, respectively. However, caution should be exercised when generalizing these results to more populated areas that also lack medical resources.

Taiwanese depression questionnaire revisit: Factor structure and measurement invariance across genders.

BACKGROUND/PURPOSE: Taiwanese Depression Questionnaire (TDQ) was widely used in Taiwan to measure individuals' proneness to depression. In light of well-established gender differences in the manifestation of depression, TDQ's structure invariance and measurement invariance across genders were examined in this study. METHODS: Data from 2604 adults was analyzed. Exploratory factor analysis was first performed to explore the factor structure. Possible factor structures and the original 2-factor structure were then compared by confirmatory factor analysis (CFA). The best fitting model was tested for measurement invariance across genders using multi-group CFA. RESULTS: EFA revealed 2 possible factor structures and suggested cross-loaded items deletion needed. This resulted in 4 models along with the original 2-factor structure to be tested in the follow-up CFA. Among the 5 models tested, the best-fitting model was the 3-factor solution with 3 cross-loaded items removed. The multi-group CFA performed on this 15-item TDQ revealed that the configural invariance, metrix invariance, and scalar invariance were all supported; partial strict invariance was supported when residual variances of items 1, 9, and 18 were set to vary. CONCLUSION: The 15-item TDQ with a 3-factor structure reflects the manifestations of depression of Taiwanese general population well. Although the results of measurement invariance suggest no gender difference in factor structure, the partial strict invariance suggests that there is gender difference in the amount of variance captured by TDQ. Hence, examining gender differences in the predictive value of different factors regarding health behaviors or medical conditions may bring fruitful results.

Simultaneous Determination of Four Triterpenoid Saponins in Aralia elata Leaves by HPLC-ELSD Combined with Hierarchical Clustering Analysis.

INTRODUCTION: Aralia elata leaves are known to have several biological activities, including anti-arrythmia, antitumor, anti-inflammatory, anti-fatigue, antimicrobial and antiviral effects. Our previous study found that triterpenoid saponins from the leaves of A. elata had antitumor effects. Quantification of the triterpenoids is important for the quality control of A. elata leaves. OBJECTIVE: To establish high-performance liquid chromatography coupled with evaporative light scattering detection (HPLC-ELSD) for the simultaneous determination of four major triterpenoid saponins, including Aralia-saponin IV, Aralia-saponin VI, 3-O-ß-d- glucopyranosyl-(1 â†’ 3)-ß-d-glucopyranosyl-(1 â†’ 3)-ß-d-glucopyranosyl oleanolic acid 28-O-ß-d-glucopyranoside (Aralia-saponin TTP)and Aralia-saponin V. METHODOLOGY: The separation was carried out on a Dikma Diamonsil C18 column (4.6 mm × 250 mm, 5 µm) efficiently with gradient elution consisting of acetonitrile and water. RESULTS: All calibration curves showed good linear regression (R2  > 0.9996) within the ranges of tested concentrations. This validated method was applied to determine the contents of the four major triterpenoid saponins in 53 samples from different regions of northeast China. Hierarchical clustering analysis was first used to classify and differentiate Aralia elata leaves. CONCLUSION: The method developed was successfully applied to analyse four major triterpenoid saponins in Aralia elata leaves which is helpful for quality control of the herb. Copyright © 2017 John Wiley & Sons, Ltd.

Simultaneous quantification of triterpenoid saponins in rat plasma by UHPLC-MS/MS and its application to a pharmacokinetic study after oral total saponin of Aralia elata leaves.

A rapid, sensitive, and reliable analytical ultra performance liquid chromatography with tandem mass spectrometry method was developed for the simultaneous determination of Aralia-saponin IV, 3-O-ß-d-glucopyranosyl-(1→3)-ß-d-glucopyranosyl-(1→3)-ß-d-glucopyranosyl oleanolic acid 28-O-ß-d-glucopyranoside, Aralia-saponin A and Aralia-saponin B after the oral administration of total saponin of Aralia elata leaves in rat plasma. Plasma samples were pretreated by protein precipitation with methanol. The analysis was performed on an ACQUITY UPLC HSS T3 column. The detection was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring mode using an electrospray ionization source with negative ionization mode. Under the experimental conditions, the calibration curves of four analytes had good linearity values (r > 0.991). The intra- and inter-day precision values of the four analytes were ≤ 11.6%, and the accuracy was between -6.2 and 4.2%.The extraction recoveries of four triterpenoid saponins were in the range of 84.06-91.66% (RSD < 10.5%), and all values of the matrix effect were more than 90.30%. The developed analytical method was successfully applied to pharmacokinetic study on simultaneous determination of the four triterpenoid saponins in rat plasma after oral administration of total saponin of Aralia elata leaves, which helps guiding clinical usage of Aralia elata leaves.

Chemical composition and biological activities of essential oil from Filifolium sibiricum (L.) Kitam.

The essential oil from Filifolium sibiricum (L.) Kitam were extracted using hydrodistillation and GC-MS was used to analyse the essential oil. The main components were espatulenol (8.55%), geranyl acetate (8.03%), caryophyllene oxide (5.47%), calamenene (4.79%), geraniol (4.28%), calamenene (4.53%), geraniol (4.06%), cedrene epoxide (3.23%), myrtenol (3.18%), transgeranylgeranio (3.13%), etc. The essential oil showed intensive inhibitory effects against MCF-7 with IC50 level of 0.78 mg/mL, HepG-2 with IC50 level of 0.44 mg/mL, SKOV-3 with IC50 level of 0.27 mg/mL, BGC-823 with IC50 level of 0.34 mg/mL. In the antibacterial test, the essential oil showed the significant antibacterial activities. The MIC and MBC values were 5.20 and 5.20 mg/mL against Staphylococcus aureus.

Determination and pharmacokinetic study of four lignans in rat plasma after oral administration of an extract of Valeriana amurensis by ultra-high performance liquid chromatography with tandem mass spectrometry.

A selective and sensitive ultra-high performance liquid chromatography with tandem mass spectrometry method was developed and validated for the determination and pharmacokinetic study of (+)-8-hydroxypinoresinol-4'-O-ß -D-glucopyranoside, prinsepiol-4-O-ß-D-glucopyranoside, (+)-pinoresinol-4,4'-di-O-ß-D-glucopyranoside, and (-)-massoniresinol 3α-O-ß-D-glucopyranoside in rat plasma after the oral administration of a Valeriana amurensis extract. The analytes and ethyl 4-hydroxybenzoate (internal standard) were separated on a Waters ACQUITY UPLC HSS T3 chromatographic column. The detection was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring mode using an electrospray ionization source operating in negative ionization mode. The linear ranges (ng/mL) of the standard curves were 0.39-154.00, 0.62-244.70, 0.50-198.60, and 0.34-134.50 for (+)-8-hydroxypinoresinol-4'-O-ß-D-glucopyranoside, prinsepiol-4-O-ß-D-glucopyranoside, (+)-pinoresinol-4,4'-di-O-ß-D-glucopyranoside, and (-)-massoniresinol 3α-O-ß-D-glucopyranoside, respectively. The inter- and intra-day precisions were less than 11.0%, the accuracies were between -5.9 and 7.7%, and the extraction recoveries of the four analytes were > 81.2% from rat plasma. The method was successfully applied to a pharmacokinetic study of the four analytes after oral administration of a Valeriana amurensis extract to rats. The developed method has the potential for pharmacokinetic analysis and to provide additional information in the clinical application of Valeriana amurensis.

Chemical composition and cytotoxicity of the essential oil from different parts of Datura metel L.

The essential oil from different parts of Datura metel L. were extracted using hydrodistillation and GC-MS was used to analyse the essential oil. The main components of flowers were ketone (23.61%) and ethyl palmitate (15.84%). The main components of leaves were ketone (18.84%) and phytol (18.71%). Ketone (39.45%) and phytol (31.32%) were the major components of petioles. Palmitic acid (30.60%) and ethyl linoleate (21.56%) were the major components of seeds. The major ingredient of roots was palmitic acid (52.61%). The main ingredients of the stems were palmitic acid (38.38%) and ethyl linoleate (17.38%). All the different parts of essential oil were screened for cytotoxicity. The roots and stems showed the inhibitory effects against HepG-2 with IC50 levels of 613.88 and 341.12 mg/L. The leaves and roots showed the inhibitory effects against HeLa with IC50 levels of 267.76 and 348.35 mg/L. All the six parts have inhibitory effects against SGC-7901 cell lines.

Role of vascular function in predicting arteriovenous fistula outcomes: an observational pilot study.

BACKGROUND: Many arteriovenous fistula (AVF) fail prior to use due to lack of maturation or thrombosis. Determining vascular function prior to surgery may be helpful to predict subsequent AVF success. This is a feasibility study to describe the vascular function in a cohort of chronic kidney disease (CKD) patients who are awaiting AVF creation. METHODS: A prospective cohort of 28 CKD patients expected to progress to HD underwent arterial stiffness (pulse wave velocity, PWV) and endothelial function testing (flow mediated dilation FMD, and peripheral arterial tonometry, PAT) one week prior to AVF creation. AVF success was defined as maintaining patency and achieving maturation. Post operative fistula assessment at 8 weeks evaluated maturation (clinical assessment of adequate fistula flowand ultrasound diameter ≥ 0.5 cm). RESULTS: The median age 72 years (62 - 78), 75% males, eGFR 15 ml/min/1.73 m(2) (12 - 18). 20 (71%) patients had successful AVF surgery with a mature AVF at 8 weeks. Patients with AVF success had higher mean PAT values 1.87 ± 0.52 than those with failed AVF 1.41 ± 0.24 p = 0.03. CONCLUSIONS: Microvascular endothelial function as measured using PAT may be useful as a predictor of AVF maturation and function. This simple non invasive marker of vascular function may be a useful tool to predict AVF outcomes.

CONTEXTE: On attribue l'échec précoce de plusieurs fistules artérioveineuses (FAV) à un manque de maturation ou à une thrombose précoce. Une évaluation de la fonction vasculaire en phase préopératoire pourrait aider à prédire l'issue d'une FAV prochaine. Ceci est une étude de faisabilité de l'évaluation de la fonction vasculaire d'une cohorte de patients atteints d'insuffisance rénale chronique (IRC) en attente de confection de FAV. MÉTHODE: L'étude de cohorte prospective comprenait 28 patients atteints d'une IRC évoluant vers des traitements d'hémodialyse. Une semaine avant la confection de la FAV, les participants ont subi des évaluations de la rigidité artérielle (analyse de l'onde de pouls) et de la fonction endothéliale (mesure de la vasodilatation médiée par le flux [flow-mediated dilatation ou FMD] et tonométrie artérielle périphérique ou EndoPAT) une semaine avant la confection de la FAV. Nous définissons le succès de la FAV comme le maintien de la perméabilité et l'atteinte de sa maturité. L'examen postopératoire de la fistule, 8 semaines après l'intervention, évaluait sa maturation (examen clinique du débit adéquat de la fistule, et évaluation du diamètre par ultrasons, soit ≥ 0,5 cm.). RÉSULTATS: L'âge moyen des participants était de 72 ans (62 ­ 78); 75% des participants étaient de sexe masculin. Le DFG estimé était de 15 ml/min/1,73 m2 (12 ­ 18). Le succès de la confection et la maturation de la FAV à 8 semaines ont été évalués auprès de 20 patients (71%). Les valeurs moyennes de l'EndoPAT étaient plus élevées chez les FAV complétées avec succès (1,87 ± 0,52), que chez les FAV en échec précoce (1,41 ± 0,24 p = 0,03). Après redressement de l'échantillon pour l'âge, le sexe et le DFG, l'EndoPAT était lié au succès de la FAV (pour chaque augmentation à l'EndoPAT, le taux de succès de la FAV était multiplié par 1,75; p = 0,02). CONCLUSIONS: La fonction microvasculaire endothéliale évaluée par EndoPAT pourrait être utilisée pour prédire la maturation et le fonctionnement d'une FAV. Cet indicateur simple et non invasif de la fonction vasculaire pourrait être également un outil pratique pour prédire le résultat de la confection d'une FAV.

Determination and pharmacokinetic study of two triterpenoid saponins in rat plasma after oral administration of the extract of Aralia elata leaves by UHPLC-ESI-MS/MS.

Aralia elata (Miq.) Seems (A. elata) grow in Northeast China and the total saponins of A. elata is used to auxiliary treatment for the acute hepatitis, chronic hepatitis and the transaminase on the high side. Aralia-saponinV and Aralia-saponinVI are the major bioactive saponins in A. elata leaves. A selective and sensitive UHPLC-MS/MS method was developed and validated for the determination and pharmacokinetic study of Aralia-saponinV and Aralia-saponinVI indwelling the extract in rat plasma in this article. The sample pretreatment involved a one-step extraction of 0.2mL plasma with methanol. Shengmaxinside C was used as internal standard (I.S.). The separation was carried out on an Agilent SB-C18 column (1.8µm, 50mm×2.1mm) at 30°C with a mobile phase of acetonitrile-5mM ammonium acetate (90:10, v/v) at a flow rate of 0.2mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via electrospray ionization (ESI) source operating in the negative ionization mode. The optimized mass transition ion-pairs (m/z) monitored for Aralia-saponinV, Aralia-saponinVI and I.S. were 1103.2/941.2, 1119.2/957.0 and 707.0/647.1, respectively. The current UHPLC-MS/MS assay method was validated for linearity, intra-day and inter-day precisions, accuracy, extraction recovery and stability, and it was suitable for the pharmacokinetic studies of the two saponins after oral administration of extract of A. elata leaves. The lower limits of quantification were 5.70ng/mL for Aralia-saponinV and 6.15ng/mL for Aralia-saponinVI. Intra-day and inter-day precisions were less than 7.4% and the accuracy range was from 1.19% to 8.60%. The mean extraction recoveries of analytes and I.S. from rat plasma were all more than 89.5%. This paper described a simple, sensitive and validated UHPLC-MS/MS method for simultaneous determination of Aralia-saponinV and Aralia-saponinVI in rat plasma after oral administration of the extract of A. elata leaves, and investigated on their pharmacokinetic studies as well.

Biological activities and potential health benefits of polysaccharides from Poria cocos and their derivatives.

Poria cocos has a long history of medicinal use in Asian countries such as China, Japan, Korea and Thailand. It is a kind of edible and pharmaceutical mushroom. The chemical compositions of Poria cocos mainly include triterpenes, polysaccharides, steroids, amino acids, choline, histidine, etc. Great advances have been made in chemical and bioactive studies on Poria cocos polysaccharides (PCP) and their derivatives in recent decades. These PCP and their derivatives exhibit many beneficial biological activities including anticancer, anti-inflammatory, antioxidant and antiviral activities. Therefore, PCP and their derivatives have great potential for further development as therapy or adjuvant therapy for cancer, immune-modulatory and antiviral drugs. This paper presents an overview of biological activities and potential health benefits of PCP and their derivatives.