Proteomic advance of ischemic stroke: preclinical, clinical, and intervention.

Ischemic stroke (IS) is the most common type of stroke and is characterized by high rates of mortality and long-term injury. The prediction and early diagnosis of IS are therefore crucial for optimal clinical intervention. Proteomics has provided important techniques for exploring protein markers associated with IS, but there has been no systematic evaluation and review of research that has used these techniques. Here, we review the differential proteins that have been found in cell- and animal- based studies and clinical trials of IS in the past 10 years; determine the key pathological proteins that have been identified in clinical trials; summarize the target proteins affected by interventions aimed at treating IS, with a focus on traditional Chinese medicine treatments. Overall, we clarify findings and problems that have been identified in recent proteomics research on IS and provide suggestions for improvements in this area. We also suggest areas that could be explored for determining the pathogenesis and developing interventions for IS.

Single-step removal of calcium, fluoride, and phenol from contaminated water by Aquabacterium sp. CZ3 via facultative anaerobic microbially induced calcium precipitation: Kinetics, mechanism, and characterization.

Confronting the complex contaminated water, Aquabacterium sp. CZ3 could perform microbially induced calcium precipitation (MICP) under facultative anaerobic condition using phenol as supplementary carbon source. Strain CZ3 exhibited a remarkable ability to remove nitrate, fluoride, calcium and phenol with removal rates of 100.00, 87.50, 66.24 and 100.00%, respectively. The Modified Gompertz model was used for kinetic analysis to determine the optimum conditions for denitrification and degradation of phenol. The mechanism of anaerobic MICP was enhanced by measuring the self-aggregation properties of the isolates. The mechanism of fluoride removal was identified as co-precipitation and adsorption by characterization analysis of the bioprecipitation. Furthermore, the changes in soluble metabolites under phenol stress explained the utilization of phenol as a co-substrate by microorganisms. This is a novel report on phenol degradation by anaerobic MICP, which provides a theoretical basis for expanding its practical application.

Transcriptome and Metabolome Analysis Provide New Insights into the Process of Tuberization of Sechium edule Roots.

Chayote (Sechium edule) produces edible tubers with high starch content after 1 year of growth but the mechanism of chayote tuberization remains unknown. 'Tuershao', a chayote cultivar lacking edible fruits but showing higher tuber yield than traditional chayote cultivars, was used to study tuber formation through integrative analysis of the metabolome and transcriptome profiles at three tuber-growth stages. Starch biosynthesis- and galactose metabolism-related genes and metabolites were significantly upregulated during tuber bulking, whereas genes encoding sugars will eventually be exported transporter (SWEET) and sugar transporter (SUT) were highly expressed during tuber formation. Auxin precursor (indole-3-acetamide) and ethylene precursor, 1-aminocyclopropane-1-carboxylic acid, were upregulated, suggesting that both hormones play pivotal roles in tuber development and maturation. Our data revealed a similar tuber-formation signaling pathway in chayote as in potatoes, including complexes BEL1/KNOX and SP6A/14-3-3/FDL. Down-regulation of the BEL1/KNOX complex and upregulation of 14-3-3 protein implied that these two complexes might have distinct functions in tuber formation. Finally, gene expression and microscopic analysis indicated active cell division during the initial stages of tuber formation. Altogether, the integration of transcriptome and metabolome analyses unraveled an overall molecular network of chayote tuberization that might facilitate its utilization.

Recognition Method of Wushu Human Complex Movement Based on Bone Point Feature.

The existing recognition methods of complex human movements in Wushu have the problem of imperfect kinetic energy model, which leads to low recognition accuracy. A complex human motion recognition method based on bone point features is designed. Identify martial arts movement posture, combine the upward movement of human center of gravity trajectory, establish the kinetic energy model of joints according to the positioning results of extremity points, set the threshold of local spatial differences of human bones with the central node of hip joint as the center point, avoid overcalculation, and optimize the complex motion identification process by combining the characteristics of bone points. Experimental Results. The correct rate of different types of actions identified by this method is 90.1% and 92.7%, and the identification time is 1.2 s and 1.41 s, which shows that this method can identify actions quickly and effectively by combining the feature information of bone points.

Multivitamin/mineral supplementation and the risk of cardiovascular disease: a large prospective study using UK Biobank data.

PURPOSE: Despite the widespread use of multivitamin/mineral supplements, the effects of multivitamin/mineral on cardiovascular disease (CVD) remain inconclusive. We aimed to prospectively investigate how multivitamin/mineral use is associated with CVD. METHODS: This population-based cohort study included 465,278 men and women who participated in the UK Biobank and were free from CVD at baseline. Participants were enrolled between 2006 and 2010 and followed-up until the end of 2018. Data on supplement use including multivitamin/mineral were collected using self-reported questionnaires. Cox proportional hazards models were used to estimate the hazard ratios of CVD events in relation to multivitamin/mineral use. RESULTS: During the follow-up, we identified 25,772 cases of CVD events, 4754 cases of CVD mortality, 18,728 cases of coronary heart disease, 6726 cases of myocardial infarction, and 4561 cases of stroke. The multivariable-adjusted hazard ratios associated with multivitamin/mineral use were 0.96 (95% CI: 0.93, 0.99) for CVD events, 0.92 (0.86, 1.00) for CVD mortality, 0.96 (0.93, 0.99) for coronary heart disease, and 0.92 (0.86, 0.97) for myocardial infarction. Subgroup analysis suggested that multivitamin/mineral use was associated with a significantly lower risk of CVD events in participants aged < 60 years and in former and current smokers (P for interaction ≤ 0.01). Sensitivity analyses showed no substantial change in the results when we excluded participants who developed CVD events during the first 2 years of follow-up. CONCLUSION: Multivitamin/mineral supplementation was associated with very modest reductions in CVD events. Age and smoking might modify these associations.

Drought resistance mechanisms of Phedimus aizoon L.

Phedimus aizoon L. is a drought-resistant Chinese herbal medicine and vegetable. However, its drought tolerant limit and the mechanism of drought tolerance are unknown, which restricts the promotion of water-saving cultivation of Phedimus aizoon L. in arid areas. To solve the above problem, we carried out a 30-day-long drought stress experiment in pots that presented different soil water contents and were divided into four groups: control check, 75-80% of the maximum water-holding capacity (MWHC); mild drought, 55-60%; moderate drought, 40-45%; and severe drought, 20-25%. The dynamic changes in both plant physiological indexes from 10 to 30 days and leaf anatomical structure on the 30th day of stress were recorded. The results show that Phedimus aizoon L. grew normally under mild drought stress for 30 days, but the growth of the plants became inhibited after 20 days of severe drought and after 30 days of moderate drought. At the same time, Phedimus aizoon L. physiologically responded to cope with drought stress: the growth of the root system accelerated, the waxy layer of the leaves thickened, and the dark reactions of the plants transformed from those of the C3 cycle to CAM. The activity of antioxidant enzymes (SOD, POD and CAT) continuously increased to alleviate the damage caused by drought stress. To ensure the relative stability of the osmotic potential, the contents of osmoregulatory substances such as proline, soluble sugars, soluble protein and trehalose increased correspondingly. Although Phedimus aizoon L. has strong drought stress resistance, our experimental results show that the soil available water content should not be less than 27% during cultivation.

[Advances on pharmacokinetics of traditional Chinese medicine under disease states].

In recent years, more and more research shows that the pharmacokinetic parameter of traditional Chinese medicine can be affected by the disease states. It's possible that drug metabolic enzymes, transporters, cell membrane permeability and the change of microbes group could be interfered with physiological and pathological changes, which enables the pharmacokinetics of traditional Chinese medicine in the body to be altered, including the process of absorption, distribution, metabolism and excretion, and then the pharmacokinetic parameters of traditional chinese medicine are altered. It's found that investigating the pharmacokinetic of traditional Chinese medicine in the pathological state is more useful than that of in normal state because the great part of traditional Chinese medicine is mainly used to treat disease. This article reflects the latest research on the pharmacokinetic of traditional Chinese medicine in the disease state such as diabete, cerebral ischemia, liver injury, inflammatory disease, nervous system disorders and fever in order to provide certain reference for clinicians designing reasonable administration dose.

Pharmacokinetic difference of berberine between normal and chronic visceral hypersensitivity irritable bowel syndrome rats and its mechanism.

Berberine is one of active alkaloids from Rhizoma coptidis in traditional Chinese medicine. The pharmacokinetics of berberine in rat plasma were compared between normal and chronic visceral hypersensitivity irritable bowel syndrome rats (CVH-IBS) established by mechanical colon irritation using angioplasty balloons for 2 weeks after oral administration of berberine hydrochloride (25 mg/kg) with the equivalent dose of 22 mg/kg for berberine according to body weight. Immunohistochemical analysis of c-fos and myosin light chain kinase (MLCK) and immunofluorescence analysis of MLCK in rat colon were conducted. Quantification of berberine in rat plasma was achieved by using a sensitive and rapid UPLC-MS/MS method. Plasma samples were collected at 15 different points in time and the pharmacokinetic parameters were analyzed by WinNonlin software. The great different pharmacokinetic behavior of berberine was observed between normal and CVH-IBS model rats. Compared with normal group, T1/2 and AUC(0-t) of berberine in the model group were significantly increased, respectively (573.21 ± 127.53 vs 948.22 ± 388.57 min; 8,657.19 ± 1,562.54 vs 11,415.12 ± 1,670.72 min.ng/ml). Cl/F of berberine in the model group significantly decreased, respectively (13.89 ± 1.69 vs 9.19 ± 2.91 L/h/kg). Additionally, the expressions of c-fos and MLCK in model group were higher than those in normal group. The pharmacokinetic behavior of berberine was significantly altered in CVH-IBS pathological conditions, which indicated the dosage modification of berberine hydrochloride in CVH-IBS were necessary. Especially, improved exposure to berberine in rat plasma in CVH-IBS model rats was attributed to increased the expression of MLCK.

Comparative pharmacokinetics of active alkaloids after oral administration of Rhizoma Coptidis extract and Wuji Wan formulas in rat using a UPLC-MS/MS method.

Wuji Wan (WJW), containing Rhizoma Coptidis (Huanglian in Chinese, HL), Frutus Evodiae Rutaecarpae (Wuzhuyu, WZY) and Radix Paeoniae Alba (Baishao, BS), is a classical traditional Chinese medical formula employed in treating intestinal disorders. Berberine (BBR) and palmatine (PMT) are the major active alkaloids in HL and have analgesic and anti-microbial effects. A sensitive, specific and validated ultra-performance liquid chromatography-tandem mass spectrometric method was developed to investigate the pharmacokinetic profiles of BBR and PMT in rat plasma and in situ intestinal perfusion solution. In comparison with the pharmacokinetic parameters of BBR and PMT, t(1/2), C(max), T(max), AUC, CL and MRT after intragastric (i.g.) administration with HL extract alone, those remarkably changed after i.g. administration with WJW formulas 1 and 2 (herb proportions are 12:2:3 and 12:1:12). Particularly, the oral bioavailability of PMT in WJW formula 1 was significantly increased. In rat intestinal perfusion experiments, the apparent permeability coefficient value of PMT was (1.45 ± 0.72) × 10(-5) cm/s when perfusion with HL was performed, and the value was significantly increased to (3.92 ± 0.52) × 10(-5) cm/s on perfusion with WJW formula 1. These results indicate that the pharmacokinetic parameters and absorption of BBR and PMT are affected by the other herbs or ingredients from WJW formulas.

Pharmacokinetics of two alkaloids after oral administration of rhizoma coptidis extract in normal rats and irritable bowel syndrome rats.

A comparative pharmacokinetic study of berberine and palmatine after oral administration of Rhizoma Coptidis extract (96 mg/kg, containing berberine 22 mg/kg and palmatine 5 mg/kg based on body weight) was performed in normal and postinflammation irritable bowel syndrome (PI-IBS) rats, induced by intracolonic instillation of acetic acid and restraint stress. Quantification of berberine and palmatine in rat plasma was achieved by using a sensitive and rapid UPLC-MS/MS method. Plasma samples were collected at 13 different time points and the pharmacokinetic parameters were analyzed by WinNonlin software. The significant differences in the pharmacokinetic behaviors, such as C max⁡, AUC(0-t), V d /F, and CL/F, of berberine and palmatine were found between normal and PI-IBS model rats. The results indicated that PI-IBS pathological conditions in rats could alter the pharmacokinetic behavior of drug. Preclinical pharmacokinetic studies are usually carried out on healthy animals. However, we should pay more attention to the fact that the change of pharmacokinetic behavior plays an important role on efficacy. It is essential to investigate the pharmacokinetics of the drug in disease status.

[Research on bioactive ingredients in rat liver after oral administration of different combinations of Wuji pill].

A L9 (3(4)) orthogonal design table to be used to get nine combinations of extraction of three herbs of Wuji pill: Coptis chinensis, Tetradium ruticarpum and Paeonia lactiflora Pall., and nine extraction of single herbs correspondingly, altogether eighteen combinations. Quantification of five representative bioactive ingredients: berberine, palmatine, evodiamine, rutaecarpine, paeoniflorin in rat liver by ultra high liquid chromatography-tandem mass spectrometry after oral administration at 2 h time point of eighteen combinations. The result shows the bioactive ingredients have different concentrations betweem different combinations and the single herb with the same dosage significantly as well as the same dose combinations. C. chinensis with evodiamine concentration of low and high dose T. ruticarpum was positively correlated. T. ruticarpum with berberine concentration of low dose C. chinensis was negatively correlated and of meddle dose C. chinensis was correlated positively. T. ruticarpum with paeoniflorin concentration of middle dose P. lactiflora was correlated positively. P. lactiflora with palmatine concentration of middle dose C. chinensis was negatively correlated and with evodiamine and rutaecarpine concentration of middle dose T. ruticarpum was negatively correlated. These shows the three single herbs interactions resulted in the differences of each ingredients concentration in rat liver. The orthogonal analysis indicates the combination 12: 6: 6 make the maximum concentration in rat liver.

Cloning and characterization of a potato StAN11 gene involved in anthocyanin biosynthesis regulation.

Anthocyanins are a class of products of plant secondary metabolism and are responsible for tubers color in potato. The biosynthesis of anthocyanins is a complex biological process, in which multiple genes are involved including structural genes and regulatory genes. In this study, StAN11, a WD40-repeat gene, was cloned from potato cultivar Chieftain (Solanum tuberosum L.). StAN11 (HQ599506) contained no intron and its open reading frame (ORF) was 1,029 bp long, encoding a putative protein of 342 amino acids. In order to verify its role in anthocyanin biosynthesis, StAN11 was inserted behind the CaMV-35S promoter of pCMBIA1304 and the recombination vector was introduced into the potato cultivar Désirée plants by Agrobacterium-mediated transformation. The color of transgenic tuber skin was significantly deepened, compared to the wild-type control, which was highly consistent with the accumulation of anthocyanin and expression of StAN11 in transgenic lines tuber skin. Further analysis on the expression of Flavonone-3-hydroxylase (F3H), Dihydroflavonol reductase (DFR), Anthocyanidin synthase (ANS), and Flavonoid 3-O-glucosyl transferase (3GT) in transgenic plants revealed that only DFR was upregulated. This result suggested that StAN11 regulated anthocyanin biosynthesis in potato by controlling DFR expression and accumulation of anthocyanin could be increased through overexpression of StAN11 in the tubers with the genetic background of anthocyanin biosynthesis.

[Effect of Shenlian extracts on blood flow and vessel pathological changes in rabbits carotid atherosclerosis model induced by low shear stress].

Lipid accumulation in the vessel wall and tunica intima vasorum pathological changes are important factors in the development of atherosclerosis, which are closely related with hemodynamics. In this paper, we established a model of local low shear stress in rabbits using carotid artery cannula and a high cholesterol diet for 2 weeks, 4 weeks and 8 weeks. The effects of Shenlian extract on blood flow, vascular pathology formation and lipid metabolism were assessed by electromagnetic blood flow meter and hematoxylin-eosin staining of the proximal end in carotid artery at different times. The results demonstrate that the relationship between blood flow and shear stress for control, atorvastatin, Shenlian extract high-dose, Shenlian extract middle-dose, and Shenlian extract low-dose were linearly related. The blood flow and the shear stress of proximal end in carotid artery of Shenlian extract (1.12, 2.24, 4.48 g x kg(-1)), and atorvastatin (4.7 x 10(-4) g x kg(-1)) were significantly (P < 0.05)increased compared with the control. Plasma total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) ,and high density lipoprotein cholesterol (HDL-C) were markedly decreased with the increasing of dose and time. This study is the first to prove that the inhibition of Shenlian extract on low shear stress (LSS) induces rabbits carotid atherosclerosis with increasing blood flow and decreasing lipids and vessel pathological changes.

[Study on metabolism of Coptis chinensis alkaloids from different compatibility of Wuji Wan in human intestinal flora].

OBJECTIVE: To study the metabolism of berberine and palmatine in prescription compatibility of Wuji Wan in human intestinal flora. METHOD: The L9 (3(4)) orthogonal design was adopted to compare prescription compatibility of nine groups of Wuji Wan composed of Coptis chinensis, Evodiae and fried Radix paeoniae alba into and single ingredient of C. chinensis. They were cultivated with fresh human excrements under anaerobic conditions for 24 h. A HPLC-UV method was adopted for determining berberine and palmatine in bacteria culture medium, in order to compare the metabolism of the two components in different prescription compatibility. RESULT: Metabolism of berberine was positively correlated with doses, whereas metabolism of palmatine was negatively correlated with doses in extracts from C. chinensis. Compound compatibility speeded up the metabolism of berberine in low dose, which was positively related to the doses of Evodiae and fried Paeoniae Alba Radix; meanwhile Compound compatibility slowed down the metabolism of berberine in high dose, which was negatively related to the dose of Evodiae. Compound compatibility speeded up the metabolism of palmatine in high dose, which was negatively related to the doses of Evodiae and fried Paeoniae Alba Radix. CONCLUSION: The metabolism of the compatibility of Wuji Wan speeds up, when Coptis chinensis components metabolite rapidly in intestinal flora; while the metabolism of the compatibility of Wuji Wan slows down, when C. chinensis components metabolite slowly in intestinal flora. Therefore, they show a balanced effect. Additionally, different proportion of C. chinensis, Evodiae and fried Paeoniae Alba Radix cause difference in metabolism speed of berberine and palmatine to some extent.

Prediction of protein structural classes by recurrence quantification analysis based on chaos game representation.

In this paper, we intend to predict protein structural classes (alpha, beta, alpha+beta, or alpha/beta) for low-homology data sets. Two data sets were used widely, 1189 (containing 1092 proteins) and 25PDB (containing 1673 proteins) with sequence homology being 40% and 25%, respectively. We propose to decompose the chaos game representation of proteins into two kinds of time series. Then, a novel and powerful nonlinear analysis technique, recurrence quantification analysis (RQA), is applied to analyze these time series. For a given protein sequence, a total of 16 characteristic parameters can be calculated with RQA, which are treated as feature representation of protein sequences. Based on such feature representation, the structural class for each protein is predicted with Fisher's linear discriminant algorithm. The jackknife test is used to test and compare our method with other existing methods. The overall accuracies with step-by-step procedure are 65.8% and 64.2% for 1189 and 25PDB data sets, respectively. With one-against-others procedure used widely, we compare our method with five other existing methods. Especially, the overall accuracies of our method are 6.3% and 4.1% higher for the two data sets, respectively. Furthermore, only 16 parameters are used in our method, which is less than that used by other methods. This suggests that the current method may play a complementary role to the existing methods and is promising to perform the prediction of protein structural classes.