Stability of tryptophan-containing LOs in flaxseed oil and their response towards γ-tocopherol.

Linusorbs (LOs), significantly influence oil quality and sensory properties of flaxseed oil. Trp-containing LOs exhibit distinct oxidative behavior when γ-tocopherol (γ-T) is present. Polar fractions of crude flaxseed oil were stripped via silica absorption, and reintroduced (LO and γ-T) separately into the oil matrix to investigate their interaction during storage. Compared with crude oil, LOs account for 18.49% reduction of p-anisidine value, while LOs with γ-T contributed to most of the endogenous antioxidant effect in crude oil. γ-T was found to suppress oxidation of Trp-containing LO at early stage (Met form), while facilitate oxidation while at their mid-stage (MetO form, Methionine sulfoxide). In vitro oxidation shows that CLD more likely cleaved into peptide fragments, while few products retain intact ring structures. LC-MS/MS analysis and silicon simulation revealed proximity between MetO and Trp residues, facilitating inter- or intra-molecular reactions and ring structure rupture. Remarkably, the presence of γ-T facilitate these phenomena.

Left ventricular global longitudinal strain using a novel fully automated method: A head-to-head comparison with a manual layer-specific strain and establishment of normal reference ranges.

BACKGROUND: A novel automated method for measuring left ventricular (LV) global longitudinal strain (GLS) along the endocardium has advantages in terms of its rapid application and excellent reproducibility. However, it remains unclear whether the available normal range for conventional GLS using the manual method is applicable to the automated GLS method. This study aimed to compare automated GLS head-to-head with manual layer-specific GLS, and to identify whether a specialized normal reference range for automated GLS is needed and explore the main determinants. METHODS: In total, 1683 healthy volunteers (men, 43%; age, 18-80 years) were prospectively enrolled from 55 collaborating laboratories. LV GLS was measured using both manual layer-specific and automated methods. RESULTS: Automated GLS was higher than endocardial, mid-myocardial, and epicardial GLS. Women had a higher automated GLS than men. GLS had no significant age dependency in men, but first increased and then decreased with age in women. Accordingly, sex- and age-specific normal ranges for automated GLS were proposed. Moreover, GLS appeared to have different burdens in relation to dominant determinants between the sexes. GLS in men showed no dominant determinants; however, GLS in women correlated with age, body mass index, and heart rate. CONCLUSIONS: Using the novel automated method, was LV GLS higher than when using the manual GLS method. The normal ranges of automated GLS stratified according to sex and age were provided, with dominant determinants showing sex disparities that require full consideration in clinical practice.

Construction and Validation of a Novel Nomogram for Predicting the Risk of Metastasis in a Luminal B Type Invasive Ductal Carcinoma Population.

Background: Postoperative distant metastasis is the main cause of death in breast cancer patients. We aimed to construct a nomogram to predict the risk of metastasis of luminal B type invasive ductal carcinoma. Methods: We applied the data of 364 luminal B type breast cancer patients between 2008 and 2013. Patients were categorized into modeling group and validation group randomly (1:1). The breast cancer metastasis nomogram was developed from the logistic regression model using clinicopathological variables. The area under the receiver-operating characteristic curve (AUC) was calculated in modeling group and validation group to evaluate the predictive accuracy of the nomogram. Results: The multivariate logistic regression analysis showed that tumor size, No. of the positive level 1 axillary lymph nodes, human epidermal growth factor receptor 2 (HER2) status and Ki67 index were the independent predictors of the breast cancer metastasis. The AUC values of the modeling group and the validation group were 0.855 and 0.818, respectively. The nomogram had a well-fitted calibration curve. The positive and negative predictive values were 49.3% and 92.7% in the modeling group, and 47.9% and 91.0% in the validation group. Patients who had a score of 60 or more were thought to have a high risk of breast cancer metastasis. Conclusions: The nomogram has a great predictive accuracy of predicting the risk of breast cancer metastasis. If patients had a score of 60 or more, necessary measures, like more standard treatment methods and higher treatment adherence of patients, are needed to take to lower the risk of metastasis and improve the prognosis.

Normal reference values for mitral annular plane systolic excursion by motion-mode and speckle tracking echocardiography: a prospective, multicentre, population-based study.

AIMS: Mitral annular plane systolic excursion (MAPSE) is a simple and reliable index for evaluating left ventricular (LV) systolic function, particularly in patients with poor image quality; however, the lack of reference values limits its widespread use. This study aimed to establish the normal ranges for MAPSE measured using motion-mode (M-mode) and two-dimensional speckle tracking echocardiography (2D-STE) and to explore its principal determinants. METHODS AND RESULTS: This multicentre, prospective, cross-sectional study included 1952 healthy participants [840 men (43%); age range, 18-80 years] from 55 centres. MAPSE was measured using M-mode echocardiography and 2D-STE. The results showed that women had a higher MAPSE than men and MAPSE decreased with age. The age- and sex-specific reference values for MAPSE were established for these two methods. Multiple linear regression analyses revealed that MAPSE on M-mode echocardiography correlated with age and MAPSE on 2D-STE with age, blood pressure (BP), heart rate, and LV volume. Moreover, MAPSE measured by 2D-STE correlated more strongly with global longitudinal strain compared with that measured using M-mode echocardiography. CONCLUSION: Normal MAPSE reference values were established based on age and sex. BP, heart rate, and LV volume are potential factors that influence MAPSE and should be considered in clinical practice. Normal values are useful for evaluating LV longitudinal systolic function, especially in patients with poor image quality, and may further facilitate the use of MAPSE in routine assessments.

Post-acute COVID-19 symptom risk in hospitalized and non-hospitalized COVID-19 survivors: A systematic review and meta-analysis.

Background: Post-acute coronavirus disease 2019 (COVID-19) symptoms occurred in most of the COVID-19 survivors. However, few studies have examined the issue of whether hospitalization results in different post-acute COVID-19 symptom risks. This study aimed to compare potential COVID-19 long-term effects in hospitalized and non-hospitalized COVID-19 survivors. Methods: This study is designed as a systematic review and meta-analysis of observational studies. A systematic search of six databases was performed for identifying articles published from inception until April 20th, 2022, which compared post-acute COVID-19 symptom risk in hospitalized and non-hospitalized COVID-19 survivors using a predesigned search strategy included terms for SARS-CoV-2 (eg, COVID, coronavirus, and 2019-nCoV), post-acute COVID-19 Syndrome (eg, post-COVID, post COVID conditions, chronic COVID symptom, long COVID, long COVID symptom, long-haul COVID, COVID sequelae, convalescence, and persistent COVID symptom), and hospitalization (hospitalized, in hospital, and home-isolated). The present meta-analysis was conducted according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement using R software 4.1.3 to create forest plots. Q statistics and the I 2 index were used to evaluate heterogeneity in this meta-analysis. Results: Six observational studies conducted in Spain, Austria, Switzerland, Canada, and the USA involving 419 hospitalized and 742 non-hospitalized COVID-19 survivors were included. The number of COVID-19 survivors in included studies ranged from 63 to 431, and follow-up data were collected through visits in four studies and another two used an electronic questionnaire, visit and telephone, respectively. Significant increase in the risks of long dyspnea (OR = 3.18, 95% CI = 1.90-5.32), anxiety (OR = 3.09, 95% CI = 1.47-6.47), myalgia (OR = 2.33, 95% CI = 1.02-5.33), and hair loss (OR = 2.76, 95% CI = 1.07-7.12) risk were found in hospitalized COVID-19 survivors compared with outpatients. Conversely, persisting ageusia risk was significantly reduced in hospitalized COVID-19 survivors than in non-hospitalized patients. Conclusion: The findings suggested that special attention and patient-centered rehabilitation service based on a needs survey should be provided for hospitalized COVID-19 survivors who experienced high post-acute COVID-19 symptoms risk.

Two Stable Cd-MOFs as Dual-Functional Materials with Luminescent Sensing of Antibiotics and Proton Conduction.

Construction and investigation of dual-functional metal-organic frameworks (MOFs) with luminescent sensing and proton conduction provide widespread applications in clean energy and environmental monitoring fields. By selecting a phosphonic acid ligand 4-pyridyl-CH2N(CH2PO3H2)2 (H4L) and coligand 2,2'-biimidazole (H2biim), two cadmium-based MOFs [Cd1.5(HL)(H2biim)0.5] (1) and (H4biim)0.5·[Cd2(L)(H2biim)Cl] (2) with different structures and properties have been hydrothermally synthesized by controlling reaction temperature. Based on the excellent thermal and chemical stabilities, and good luminescent stabilities in water solution, 1 and 2 can serve as luminescent sensors of chloramphenicol (CAP) with different quenching constant (KSV) values and detection limits (LODs) in water, simulated environmental system, and real fish water system. Meanwhile, different sensing effects and possible sensing mechanisms are analyzed in detail. Moreover, 1 and 2 can also serve as good proton-conducting materials. The proton conductivities can reach up to 1.41 × 10-4 S cm-1 for 1 and 1.02 × 10-3 S cm-1 for 2 at 368 K and 95% relative humidity (RH). Among them, 2 shows better luminescent sensing and proton conduction performance than 1, which indicates that different crystal structures have a great impact on the properties of MOFs. Through the discussion of the relationship between structures and properties in detail, the possible reasons for the differences in properties are obtained, which can provide theoretical guidance for the rational design of this kind of dual-functional MOFs in the future.

Identification of Candidate Genes Related to Synovial Macrophages in Rheumatoid Arthritis by Bioinformatics Analysis.

OBJECTIVE: Rheumatoid arthritis (RA) is one of the most prevalent inflammatory arthritis worldwide. However, the genes and pathways associated with macrophages from synovial fluids in RA patients still remain unclear. This study aims to screen and verify differentially expressed genes (DEGs) related to identifying candidate genes related to synovial macrophages in rheumatoid arthritis by bioinformatics analysis. METHODS: We searched the Gene Expression Omnibus (GEO) database, and GSE97779 and GSE10500 with synovial macrophages expression profiling from multiple RA microarray dataset were selected to conduct a systematic analysis. GSE97779 included nine macrophage samples from synovial fluids of RA patients and five macrophage samples from primary human blood of HC. GSE10500 included five macrophage samples from synovial fluids of RA patients and three macrophage samples from primary human blood of HC. Functional annotation of DEGs was performed, including Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Protein-protein interaction (PPI) network of DEGs was established using the STRING database. CytoHubba was used to identify hub genes. MCODE was used to determine gene clusters in the interactive network. RESULTS: There were 2638 DEGs (1425 upregulated genes and 1213 downregulated ones) and 889 DEGs (438 upregulated genes and 451 downregulated ones) selected from GSE97779 and GSE10500, respectively. Venn diagrams showed that 173 genes were upregulated and 106 downregulated in both two datasets. The top 10 hub genes, including FN1, VEGFA, HGF, SERPINA1, MMP9, PPBP, CD44, FPR2, IGF1, and ITGAM, were identified using the PPI network. CONCLUSION: This study provides new insights for the potential biomarkers and the relevant molecular mechanisms in RA patients. Our findings suggest that the 10 candidate genes might be used in diagnosis, prognosis, and therapy of RA in the future. However, further studies are required to confirm the expression of these genes in synovial macrophages in RA and control specimen.

Discovery of a Potential Liver Fibrosis Inhibitor from a Mushroom Endophytic Fungus by Genome Mining of a Silent Biosynthetic Gene Cluster.

Liver fibrosis has accounted for liver diseases and overall mortality, but no relevant drug has been developed. Filamentous fungi are important resources of natural products for pharmaceutical development. Calcarisporium arbuscula is a mushroom endophytic fungus, which primarily produces aurovertins. Here, in an aurovertin null-production mutant, one silent gene cluster (mca17) was activated by overexpression of a pathway-specific zinc finger transcriptional regulator, and a tetramic acid-type compound (1, MCA17-1) was identified. Along with detailed structural characterization, its biosynthesis was proposed to be produced from the core PKS-NRPS hybrid enzyme. Moreover, 1 suppressed the activation of LX-2 upon transforming growth factor-ß (TGF-ß) challenge and had stronger bioactivity than the positive control obeticholic acid (OCA) against liver fibrosis. Our work suggested that this engineered fungus could be a producer of 1 for promising pharmaceutical development, and alternatively, it would be developed as a mushroom ingredient in dietary therapy to prevent liver fibrosis.

Synthetic cajaninstilbene acid derivatives eradicate methicillin-resistant Staphylococcus aureus persisters and biofilms.

The Staphylococcus aureus can switch to a transient genotype-invariant dormancy, known as a persister, to survive treatment with high doses of antibiotics. This transient persister is an important reason underlying its resistance. There is an urgent need to find new antibacterial agents capable of eradicating methicillin-resistant S. aureus (MRSA) persisters. In this study, 37 new derivatives of cajaninstilbene acid (CSA) were designed and synthesized, and their biological activity against MRSA persisters was evaluated. Most of the newly synthesized derivatives exhibit more potent antimicrobial properties against S. aureus and MRSA than CSA itself, and 23 of the 37 derivatives show a tendency to eradicate MRSA persisters. A representative compound (A6) was demonstrated to target bacterial cell membranes. It eradicated the adherent biofilm of MRSA in a concentration dependent manner, and showed a synergistic antibacterial effect with piperacilin. In a model mouse abscess caused by MRSA persisters, A6 effectively reduced the bacterial load in vivo. These results indicate that A6 is a potential candidate for treatment of MRSA persister infections.

Incremental value of three-dimensional and contrast echocardiography in the evaluation of endocardial fibroelastosis and multiple cardiovascular thrombi: A case report.

BACKGROUND: Endocardial fibroelastosis (EFE) is a rare heart disease characterized by thickening of the endocardium caused by massive proliferation of collagenous and elastic tissue, usually leading to impaired cardiac function. Multimodality cardiovascular imaging for the evaluation of EFE with thrombi is even rarer. CASE SUMMARY: We report a rare case of EFE associated with multiple cardiovascular thrombi. Three-dimensional (3D) and contrast echocardiography (CE) were used to assess ventricular thrombi. Anticoagulant therapy was administered to eliminate the thrombi. The peripheral contrast-enhanced thrombi with the highest risk were dissolved with anticoagulant therapy at the time of reexamination, which was consistent with the presumption of fresh loose thrombi. CONCLUSION: This new echocardiography technique has a great advantage in the diagnosis and treatment of EFE. On the basis of conventional echocardiography, 3D echocardiography is used to display the position, shape, and narrow base of the thrombus. CE does not only help to confirm the diagnosis of thrombus, but also determines its risk.

A Cell Factory of a Fungicolous Fungus Calcarisporiumarbuscula for Efficient Production of Natural Products.

Fungal natural products are rich sources of clinical drugs. Particularly, the fungicolous fungi have a large number of biosynthetic gene clusters (BGCs) to produce numerous bioactive natural products, but most BGCs are silent in the laboratory. We have shown that a fungicolous fungus Calcarisporiumarbuscula NRRL 3705 predominantly produces the highly reduced polyketide-type mycotoxins aurovertins. Here after evaluation of the aurovertin-null mutant ΔaurA as an efficient host, we further screened two strong promoters aurBp and A07068p based on RNA-Seq, and successfully activated an endogenous gene cluster from C. arbuscula as well as three additional exogenous BGCs from other fungi to produce polyketide-type natural products. Thus, we showed an efficient expression system from the fungicolous fungus C. arbuscula, which will be highly beneficial and complementary to the conventional Aspergillus and Penicillium fungal cell factories, and provides a useful toolkit for genome-wide mining of bioactive natural products from fungicolous fungi.

Cajaninstilbene acid analogues as novel quorum sensing and biofilm inhibitors of Pseudomonas aeruginosa.

Biofilm formation and virulence factor secretion in opportunistic pathogen Pseudomonas aeruginosa are essential for establishment of chronic and recurrent infection, which are regulated by quorum sensing (QS) system. In this study, a set of cajaninstilbene acid analogues were designed and synthesized, and their abilities to inhibit QS and biofilm formation were investigated. Among all the compounds, compounds 3g, 3m and 3o showed potent anti-biofilm activity, especially 3o exhibited promising biofilm inhibitory activity with biofilm inhibition ratio of 49.50 ± 1.35% at 50 µM. Three lacZ reporter strains were constructed to identify the effects of compound 3o on different QS systems. Compound 3o showed the suppression on the expression of lasB-lacZ and pqsA-lacZ as well as on the production of their corresponding virulence factors. Therefore, compound 3o is expected to be generated as a lead compound with inhibition of biofilm formation and QS of Pseudomonas aeruginosa.

The design of a novel near-infrared fluorescent HDAC inhibitor and image of tumor cells.

Histone deacetylases (HDACs) have been found to be biomarkers of cancers and the corresponding inhibitors have attracted much attention these years. Herein we reported a near-infrared fluorescent HDAC inhibitor based on vorinostat (SAHA) and a NIR fluorophore. This newly designed inhibitor showed similar inhibitory activity to SAHA against three HDAC isoforms (HDAC1, 3, 6). The western blot assay showed significant difference in compared with the negative group. When used as probe for further kinematic imaging, Probe 1 showed enhanced retention in tumor cells and the potential of HDAC inhibitors in drug delivery was firstly brought out. The cytotoxicity assay showed Probe 1 had some anti-proliferation activities with corresponding IC50 values of 9.20 ± 0.96 µM on Hela cells and 5.91 ± 0.57 µM on MDA-MB-231 cells. These results indicated that Probe 1 could be used as a potential NIR fluorescent in the study of HDAC inhibitors and lead compound for the development of visible drugs.

Multi-omics association analysis revealed the role and mechanism of epialleles in environmental adaptive evolution of Arabidopsis thaliana.

Epialleles, generally referring to alleles whose expression is altered due to differential DNA methylation levels, have important roles in plant morphology, development, and various physiological processes. However, the influence of environmental factors on the plant epialleles under natural conditions is unclear. Meanwhile, the role and mechanism of epialleles in the environmental adaptive evolution of plants remain elusive. In this study, we collected the transcriptome, methylome and climate data from 623 Arabidopsis accessions, derived from worldwide distributions. Then the data were subject to multi-omics association analysis combined with protein interaction network and gene enrichment analysis to identify epialleles related to specific environmental factors and to explore their possible mechanisms involved in the environmental adaptive evolution of Arabidopsis thaliana. We focused on spring and summer precipitation and identified five potential epialleles with differential DNA methylation levels located in specific regions of the genes: AGL36, AT2G34100, AT4G09360, LSU4 and AT5G56910. Interestingly, the imprinted gene AGL36 related to seed development was discovered as an epiallele involved in the environmental adaptive evolution of Arabidopsis thaliana, and the other four genes are related to the response to biotic stress. By protein interaction, GO enrichment, and KEGG pathway analysis, we also found that LSU4 may participate in the sulfur metabolism network like other members of the LSU gene family, and be involved in the biotic stress response by affecting glucosinolate metabolism. In natural conditions low precipitation may affect the severity of local pests and diseases. Therefore, we speculate that DNA methylation associates with the expression of the four genes to regulate the resistance of Arabidopsis thaliana to local pests and diseases, and ultimately participates in the adaptation to local environments.

Design, synthesis and biological evaluation of 2-substituted 3-hydroxy-6-methyl-4H-pyran-4-one derivatives as Pseudomonas aeruginosa biofilm inhibitors.

Drug-resistant bacteria associated with biofilm formation are rapidly on the rise, requiring novel therapeutic options to combat biofilm induced drug-resistance. In this study, a class of 3-hydroxy-2-(phenylhydroxy-methyl)-6-methyl-4H-pyran-4-one derivatives (1a-1e) were found by screening of an in-house compound library to be potential Pseudomonas aeruginosa biofilm inhibitors. Thirty one novel 2-substituted 3-hydroxy-6-methyl-4H-pyran-4-one derivatives were synthesized and assayed for their biofilm inhibitory activity. A promising biofilm inhibitor 6a was identified, and showed an obvious biofilm inhibitory effect even at a concentration of 2.5 µM. Further mechanism studies revealed that 6a only shows inhibitory effects on the expression of pqsA-gfp in a fluorescent reporter strain, and the production of a PQS- regulated virulence factor, pyocyanin. This indicates that this type of compound exercises its anti-biofilm activity specifically through the PQS pathway. Novel chemical biofilm inhibitors are described here and guard against biofilm formation associated with Pseudomonas aeruginosa infections.

[Rhizosphere Microbial Diversity in Different Wetland Microcosms].

To investigate the rhizosphere microbial community structure characteristics in varying combinations of plants and filter materials in the process of aquaculture pond water treatment, six types of wetland microcosms were established using two kinds of plants (Zizania latifolia Turcz. and Sagittaria graminea) and two types of filter materials (garnet and magnetite). High-throughput sequencing technology was used to analyze the microbial structural features and composition diversity of the wetland rhizosphere. The results were as follows. The microorganisms recovered belonged to 52 phyla, 118 classes, 455 families, 905 genera, and 1426 species. Based on the Shannon index, Zizania latifolia Turcz. (average value: 5.77) had a higher capacity than Sagittaria graminea(average value: 5.29) in terms of microbial enrichment. However, the rate of Proteobacteria in the rhizosphere microorganism communities of the Sagittaria graminea and Zizania latifolia Turcz. microcosms were 61.97% and 51.78%, respectively, further showing that the roots of Sagittaria graminea in the wetland microcosms better enriched the Proteobacteria during the experimental period. The major bacterial groups of different plant roots were enriched with ß-Proteobacteria in the experiment. The results of this study provide a theoretical basis for species optimization in artificial wetland systems and best combination of wetland construction that will be useful for future investigations.

Cardioprotection of ginsenoside Rb1 against ischemia/reperfusion injury is associated with mitochondrial permeability transition pore opening inhibition.

OBJECTIVE: To investigate the role of ginsenoside Rb1 (Gs-Rb1) in cardioprotection against ischemia/reperfusion (I/R) or hypoxia/reoxygenation (H/R) injury and to explore whether the cardioprotective action is mediated via attenuating the formation of mitochondrial permeability transition pore (mPTP). METHODS: A Langendorff-perfused model of rat heart was employed. I/R injury was induced by breaking off perfusion for 40 min then reperfusion for 60 min. Gs-Rb1 (100 µmol/L) were administrated for 10 min before I/R. Infarct size was estimated by the 2,3,5-triphenyl tetrazolium chloride (TTC) staining. Lactate dehydrogenase (LDH) and creatine kinase (CK) released from effluents were measured. Transmission electron microscopy was performed to assess morphological difference between cardiac mitochondrial isolated from I/R rats and Gs-Rb1 pretreated rats. Western blot analysis was used to determine phosphorylation of protein kinase B/Akt, and its downstream target glycogen synthase kinase 3ß (GSK-3ß). Incubation isolated cardiac mitochondria with Gs-Rb1, Ca2+-induced opening of the mPTP was assessed by the reduction of absorbance at 520 nm (A520). Neonatal rat cardiomyocytes were subjected to hypoxia 9 h followed by reoxygenation 4 h to induce H/R injury. After pretreated with different concentration of Gs-Rb1 (6.25, 25, 100 µmol/L ), cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) method. The membrane potential was estimated by Rh123 fluorescence. mPTP opening was measured using the probe calcein-AM. RESULTS: Gs-Rb1 100 µmol/L significantly reduced the infarct size of hearts (26.39%±11.67% vs. I/R group 56.68%±5.88%, P<0.01). Compared with the I/R group, Gs-Rb1 pretreatment decreased LDH and CK levels in the coronary effluent (P<0.05 or P<0.01) as well as attenuated destructive ultrastructure induced by I/R. The protective effect of Gs-Rb1 involved in phosphorylating protein kinase B/PKB (Akt) and GSK-3ß. In mitochondria isolated from rat hearts, significant inhibition of Ca2+-induced swelling was observed in samples that were pretreated with Gs-Rb1 (6.25, 25, 100, 400 µmol/L) for 10 min. When cardiomyocytes were isolated from neonatal rat and subjected to H/R, cell viability was increased with treatment of Gs-Rb1 (6.25, 25, 100 µmol/L ). Gs-Rb1 inhibited mPTP opening and restored subsequent loss of mitochondrial membrane potential. CONCLUSION: Gs-Rb1 presents cardioprotective effect against I/R or H/R injury which involves in activating Akt, phosphorylating GSK-3ß and inhibiting mPTP opening.

Association of apolipoprotein E (ApoE) polymorphisms with risk of primary hyperuricemia in Uygur men, Xinjiang, China.

BACKGROUND: Apolipoprotein E (ApoE) participates in lipoprotein metabolism and immune regulation. This study assessed association between ApoE polymorphisms with hyperuricemia and uric acid metabolism in Uygur men, Xinjiang, China. METHODS: A total of 474 hyperuricemia patients and 518 healthy male controls were recruited from the Health Screening Center, Uygur region of Xinjiang, China and subjected to ApoE genotyping using a multiplex amplification refractory mutation system PCR. RESULTS: Apolipoprotein E3/3 genotype was the predominant type with a frequency of 67.7%, while E2/2 was lower than E4/4 in Uygur males. The frequencies of ApoE2, E3, and E4 alleles were 8.5%, 80.1% and 11.4%, respectively. Distribution of ApoE genotypes was significantly different in hyperuricemia patients from the healthy controls (p<0.001). Particularly, the frequency of ApoE E3/3 was 71.7%, E2/3 9.3%, E3/4 9.3%, E4/4 3.2%, E2/4 2.3%, and E2/2 0.2% in patients vs. 68.1%, 4.6%, 2.9%, 12%, 0.6%, and 4.6% in controls, respectively. Moreover, frequency of ApoE E2 allele was greater in the healthy controls than in patients (p<0.001) and the highest level of uric acid occurred in those with ApoE2/4 and E3/4 genotypes, whereas the lowest uric acid level occurred in those with ApoE E2/2 genotype. In addition, the subjects with the ApoE2 allele had a lower uric acid and LDL-C level than those with the ApoE3 allele and ApoE4 allele (p<0.05). The risk of developing hyperuricemia in subjects without the ApoE2 allele was 1.7 fold higher than those subjects with the ApoE2 allele. CONCLUSIONS: This study revealed frequencies and distributions of ApoE alleles and genotypes in Uygur males, which are different from Han Chinese. ApoE E4 was associated with a slightly higher risk of primary hyperuricemia, whereas ApoE E2 was associated with reduced risk of primary hyperuricemia and LDL-C level.

The coronary dilation effect of shen fu injection was mediated through NO.

OBJECTIVES: Shen Fu Injection (SF), which consisted of Red ginseng extraction injection (RG) and prepared aconite extraction injection (RA), is a traditional Chinese medicine mainly used for various cardiac diseases. This study is to analyse SF's effects on cardiac performance and coronary circulation. And the coronary dilating effect and mechanism of the above three injections were also explored. METHODS: Mature male guinea pigs were used as our animal model. We employed two types of perfusion methods (constant pressure and constant flow) in vitro, using Langendorff heart preparations to observe the cardiac function and coronary response to SF (1/200). The coronary dilation effects of the above three injections (1/800, 1/400 and 1/200) were recorded at basal coronary resting tone and when coronary vessels were pre-contracted with a thromboxane A2 analogue (U46619), in the presence or the absence of the inhibitor of nitric oxide synthesis (L-NAME, 10-4 M), the blocker of Ca2+-activated potassium channel(TEA, 10-3 M), or the blocker of adenosine triphosphate (ATP)-sensitive potassium channel (glybenclamide) (10-5 M). RESULTS: When perfused with constant pressure, SF significantly increased coronary flow, left ventricular developed pressure (LVDP) and the rate-pressure product (RPP). When perfused with constant flow, SF produced a significant reduction in the coronary perfusion pressure (CPP), LVDP and RPP. The coronary vasodilatation response of the above three injections can be reduced by L-NAME but was unaffected by TEA or glybenclamide when coronary vessels were pre-contracted with U46619 but not at resting tone. SF, RG and RA can all up-regulate eNOS expression in the human umbilical vein cells (EA.hy926). CONCLUSION: We demonstrated that SF does not contribute to the inotropic change of myocardium whose improvement is due to alternation of coronary flow. The coronary dilation effect of SF was mediated through RG and RA, via promoting NO release.

Modified coaxial electrospinning for the preparation of high-quality ketoprofen-loaded cellulose acetate nanofibers.

This study investigates the use of a modified coaxial electrospinning process in the production of drug-loaded cellulose acetate (CA) nanofibers. With CA employed as a filament-forming matrix and ketoprofen (KET) as an active pharmaceutical ingredient, modified coaxial processes using sheath fluids comprising only mixed solvents were undertaken. With a sheath-to-core flow rate ratio of 0.2:1, the nanofibers prepared from the coaxial process had a smaller average diameter, narrower size distribution, more uniform structures, and smoother surface morphologies than those generated from single fluid electrospinning. In addition, the coaxial fibers provided a better zero-order drug release profile. The use of a sheath solvent means that the core jet is subjected to electrical drawing for a longer period, facilitating homogeneous core jet solidification and retarding the formation of wrinkles on the surface of the nanofibers. This modified coaxial electrospinning protocol allows the systematic fabrication of functional polymer nanofibers with improved quality.