CENPA functions as a transcriptional regulator to promote hepatocellular carcinoma progression via cooperating with YY1.

The centromere proteins (CENPs), a critical mitosis-related protein complexes, are involved in the kinetochore assembly and chromosome segregation. In this study, we identified that CENPA was significantly up-regulated in HCC and highly expressed CENPA correlated with poor prognosis for HCC patients. Knockdown of CENPA inhibited HCC cell proliferation and tumor growth in vitro and in vivo. Mechanistically, CENPA transcriptionally activated and cooperated with YY1 to drive the expression of cyclin D1 (CCND1) and neuropilin 2 (NRP2). Moreover, we identified that CENPA can be lactylated at lysine 124 (K124). The lactylation of CENPA at K124 promotes CENPA activation, leading to enhanced expression of its target genes. In summary, CENPA function as a transcriptional regulator to promote HCC via cooperating with YY1. Targeting the CENPA-YY1-CCND1/NRP2 axis may provide candidate therapeutic targets for HCC.

Brequinar inhibits African swine fever virus replication in vitro by activating ferroptosis.

BACKGROUND: African swine fever virus (ASFV) is one of the most fatal swine etiological agents and has a huge economic impact on the global pork industry. Given that no effective vaccines or anti-ASFV drugs are available, there remains a pressing need for novel anti-ASFV drugs. This study aimed to investigate the anti-African swine fever virus (ASFV) activity of brequinar, a DHODH inhibitor. METHODS: The anti-ASFV activity of brequinar was investigated using IFA, HAD, HAD50, qRT-PCR, and western blotting assays. The western blotting assay was used to investigate whether brequinar inhibits ASFV replication by killing ASFV particles directly or by acting on cell factors. The confocal microscopy and western blotting assays were used to investigate whether brequinar inhibits ASFV replication by activating ferroptosis. RESULTS: In this study, brequinar was found to effectively inhibit ASFV replication ex vivo in porcine alveolar macrophages (PAMs) in a dose-dependent manner. In kinetic studies, brequinar was found to maintain ASFV inhibition from 24 to 72 hpi. Mechanistically, the time-of-addition assay showed that brequinar exerted anti-ASFV activity in all treatment modes, including pre-, co-, and post-treatment rather than directly killing ASFV particles. Notably, FerroOrange, Mito-FerroGreen, and Liperfluo staining experiments showed that brequinar increased the accumulation of intracellular iron, mitochondrial iron, and lipid peroxides, respectively. Furthermore, we also found that ferroptosis agonist cisplatin treatment inhibited ASFV replication in a dose-dependent manner and the inhibitory effect of brequinar on ASFV was partially reversed by the ferroptosis inhibitor ferrostatin-1, suggesting that brequinar activates ferroptosis to inhibit ASFV replication. Interestingly, exogenous uridine supplementation attenuated the anti-ASFV activity of brequinar, indicating that brequinar inhibits ASFV replication by inhibiting DHODH activity and the depletion of intracellular pyrimidine pools; however, the induction of ferroptosis by brequinar treatment was not reversed by exogenous uridine supplementation, suggesting that brequinar activation of ferroptosis is not related to the metabolic function of pyrimidines. CONCLUSIONS: Our data confirm that brequinar displays potent antiviral activity against ASFV in vitro and reveal the mechanism by which brequinar inhibits ASFV replication by activating ferroptosis, independent of inhibiting pyrimidine synthesis, providing novel targets for the development of anti-ASFV drugs.

Brain-Targeting Emodin Mitigates Ischemic Stroke via Inhibiting AQP4-Mediated Swelling and Neuroinflammation.

Failure to achieve target-specific delivery to ischemic brain sites has hampered the clinical efficacy of newly developed therapies for ischemic stroke. Emodin, an active ingredient isolated from traditional Chinese medicine, has been indicated to alleviate ischemic stroke; however, the underlying mechanism remains unclear. In this study, we aimed to achieve brain-targeted delivery of emodin to maximize its therapeutic efficacy and elucidate the mechanisms by which emodin alleviates ischemic stroke. A polyethylene glycol (PEG)/cyclic Arg-Gly-Asp (cRGD)-modified liposome was used to encapsulate emodin. TTC, HE, Nissl staining, and immunofluorescence staining were employed to evaluate the therapeutic efficacy of brain-targeting emodin in MCAO and OGD/R models. Inflammatory cytokine levels were determined using ELISA. Immunoprecipitation, immunoblotting, and RT-qPCR were utilized for clarifying the changes in key downstream signaling. Lentivirus-mediated gene restoration was employed to verify the core effector of emodin for relieving ischemic stroke. Encapsulating emodin in a PEG/cRGD-modified liposome enhanced its accumulation in the infarct region and substantially raised its therapeutic efficacy. Furthermore, we demonstrated that AQP4, the most abundant water transporter subunit expressed in astrocytes, plays a crucial role in mediating the mechanisms by which emodin inhibits astrocyte swelling, neuroinflammatory blood-brain barrier (BBB) breakdown in vivo and in vitro, and brain edema in general. Our study unveiled the critical target of emodin responsible for alleviating ischemic stroke and a localizable drug delivery vehicle in the therapeutic strategy for ischemic stroke and other brain injuries.

[Dissolution test and evaluation of Guizhi Fuling Capsules].

Because of the complex components, simple content determination can hardly reflect the overall quality of Guizhi Fuling Capsules. Therefore, it is necessary to carry out a multi-component dissolution test. The variability of quality among different batches of products from different manufacturers is a common problem of Chinese medicine solid preparations. To comprehensively control the quality of Guizhi Fuling Capsules, we studied the dissolution behaviors of 7 index components in the capsules under different conditions, and investigated the consistency of dissolution behaviors among different batches of products from the same manufacturer. The basket method of general rule 0931 in Chinese Pharmacopoeia was adopted, and the rotating speeds were set at 50, 75, and 100 r·min~(-1), respectively. The hydrochloric acid solution(pH 1.2), acetate buffer solution(pH 4.0), pure water, and phosphate buffer solution(pH 6.8) were used as the dissolution media. Automatic sampling was carried out at the time points of 5, 10, 20, 30, 45, and 60 min, respectively. The cumulative dissolution of 7 index components was measured through ultra-performance liquid chromatography(UPLC). The difference factor f_1 and similarity factor f_2 were calculated to comprehensively evaluate the similarity of the dissolution curves among 8 batches of Guizhi Fuling Capsules, and a variety of dissolution and release equations were fitted. The results showed that multiple components had faster dissolution rates at higher rotating speed and in hydrochloric acid medium. The 8 batches of Guizhi Fuling capsules showed the average f_1 value lower than 15 and the average f_2 value higher than 50, which indicated that different batches of products had similar dissolution behaviors. Most components had synchronous dissolution behaviors and similar release cha-racteristics. This study provides a reference for the quality consistency evaluation among batches, processing optimization, and dosage form improvement of Guizhi Fuling Capsules.

Influence of social and environmental drivers on nutrient concentrations and ratios in lakes: A comparison between China and Europe.

Global anthropogenic flows of nitrogen (N) and phosphorus (P) have exceeded planetary boundaries with significant implications for pollution of the freshwater resources in the world. Understanding the global patterns and drivers of N and P concentrations and their ratios in the lakes could help design more effective management and remediation strategies to mitigate the impacts of eutrophication. While a suite of drivers are associated with the sources of nutrients, their transport and internal processes that control concentrations of N and P in the lakes, much less is known about the relative importance of different drivers in explaining spatial variations of lake nutrients and ratios. In this study, we compared N and P concentrations and their ratios in the lakes across China and Europe and examined the differences of dominant environmental and social drivers on lake nutrients. Our comparison showed that total nitrogen (TN) and total phosphorus (TP) concentrations were much higher in the lakes in China compared to those in Europe (i.e., TN: 1.13 mg/L in China vs. 0.64 mg/L in Europe; TP: 35.83 µg/L in China vs. 19.38 µg/L in Europe, the median value). However, lake N/P ratios for both regions were not statistically different. Concentrations of TN and TP showed decoupling in both regions, with the majority of lakes having high N/P mass ratios when evaluated by the commonly accepted threshold of 23 (i.e., 61% in China and 68% in Europe), indicating that phytoplankton are more P limited relative to N. Agricultural activity in the lake catchment is an important predictor for both nutrient concentrations and their ratio in Europe. This reflects successful investments in infrastructure and policy prescriptions in addressing point sources of pollution. In comparison, lake depth and water residence time are important in the decoupling of N and P concentrations in China. The regional difference between the dominant drivers can provide important insights into development of effective water pollution control measures. It is necessary for policy makers and water resource managers to be aware of large-scale imbalance of nutrients in lake due to the potential environmental consequences. A set of spatially flexible policies for water quality controls would be beneficial for sustaining the ecological integrity and future health of lakes.

Jinwujiangu Capsule Treats Fibroblast-Like Synoviocytes of Rheumatoid Arthritis by Inhibiting Pyroptosis via the NLRP3/CAPSES/GSDMD Pathway.

Jinwujiangu capsule (JWJGC) is a traditional Chinese medicine formula used to treat rheumatoid arthritis (RA). However, whether its mechanism is associated with pyroptosis remains unclear. In this study, the ability of JWJGC to inhibit the growth of fibroblast-like synoviocytes of RA (RA-FLS) through pyroptosis was evaluated. The cells isolated from patients with RA were identified by hematoxylin and eosin (H&E) staining, immunohistochemistry, and flow cytometry. After RA-FLS were treated with different concentrations of JWJGC-containing serum, the cell proliferation inhibition rate, expression of caspase-1/3/4/5, NOD-like receptor protein 3 (NLRP3), gasdermin-D (GSDMD), and apoptosis-associated speck-like protein containing a CARD (ASC), concentrations of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18), the activity of lactic dehydrogenase (LDH), and pyroptosis were evaluated. The results showed that JWJGC increased the proliferative inhibition rate, decreased the expression of caspase-1/3/4/5, GSDMD, NLRP3, and ASC, suppressed the expression of IL-1ß and IL-18, induced the activity of LDH, and downregulated the number of double-positive FITC anti-caspase-1 and PI. Generally, our findings suggest that JWJGC can regulate NLRP3/CAPSES/GSDMD in treating RA-FLS through pyroptosis.

Immobilization of 6-O-α-maltosyl-ß-cyclodextrin on the surface of black phosphorus nanosheets for selective chiral recognition of tyrosine enantiomers.

A novel chiral sensing platform, 6-O-α-maltosyl-ß-cyclodextrin (Mal-ßCD)-based film, is proposed for selective electrochemical recognition of tyrosine (Tyr) enantiomers. Black phosphorus nanosheets (BP NSs) and Mal-ßCD modified glassy carbon electrode (Mal-ßCD/BP NSs/GCE) were prepared by a layer-to-layer drop-casting method, and the platform was easy to fabricate and facile to operate. It is proposed that the amino and hydroxyl groups of the Tyr enantiomers and the chiral hydroxyl groups of Mal-ßCD selectively form intermolecular hydrogen bonds to dominate effective chiral recognition. Two linear equations of Ip (µA) = 11.40 CL-Tyr (mM) + 0.28 (R2 = 0.99147) and Ip (µA) = 7.96 CD-Tyr (mM) + 0.22 (R2 = 0.99583) in the concentration range 0.01-1.00 mM have been obtained. The limits of detection (S/N=3) for L-Tyr and D-Tyr were 4.81 and 6.89 µM, respectively. An interesting phenomenon was that the value of IL-Tyr/ID-Tyr (1.51) in this work was slightly higher than the value of IL-Trp/ID-Trp (1.49) reported in our previous study, where tryptophan (Trp) enantiomers were electrochemically recognized by Nafion (NF)-stabilized BPNSs-G2-ß-CD composite. The two similar sensors fabricated by different methods showed different recognition ability toward either Tyr or Trp enantiomers, and the underlying mechanism was discussed in detail. More importantly, the proposed chiral sensor enables prediction of the percentages of D-Tyr in racemic Tyr mixtures. The chiral sensor may provide a novel approach for the fabrication of novel chiral platforms in the practical detection of L- or D-enantiomer in racemic Tyr mixtures.Graphical abstract.

Distribution of tyrosine-hydroxylase-immunoreactive neurons in the hypothalamus of tree shrews.

The tree shrew (Tupaia belangeri chinensis) is the closest living relative of primates. Yet, little is known about the anatomical distribution of tyrosine hydroxylase (TH)-immunoreactive (ir) structures in the hypothalamus of the tree shrew. Here, we provide the first detailed description of the distribution of TH-ir neurons in the hypothalamus of tree shrews via immunohistochemical techniques. TH-ir neurons were widely distributed throughout the hypothalamus of tree shrew. The majority of hypothalamic TH-ir neurons were found in the paraventricular hypothalamic nucleus (PVN) and supraoptic nucleus (SON), as was also observed in the human hypothalamus. In contrast, rare TH-ir neurons were localized in the PVN and SON of rats. Vasopressin (AVP) colocalized with TH-ir neurons in the PVN and SON in a large number of neurons, but oxytocin and corticotropin-releasing hormone did not colocalize with TH. In addition, colocalization of TH with AVP was also observed in the other hypothalamic regions. Moreover, TH-ir neurons in the PVN and SON of tree shrews expressed other dopaminergic markers (aromatic l-amino acid decarboxylase and vesicular monoamine transporter, Type 2), further supporting that TH-ir neurons in the PVN and SON were catecholaminergic. These findings provide a detailed description of TH-ir neurons in the hypothalamus of tree shrews and demonstrate species differences in the distribution of this enzyme, providing a neurobiological basis for the participation of TH-ir neurons in the regulation of various hypothalamic functions.

Formononetin, J1 and J2 have different effects on endothelial cells via EWSAT1-TRAF6 and its downstream pathway.

Formononetin is a natural isoflavone compound found mainly in Chinese herbal medicines such as astragalus and red clover. It is considered to be a typical phytooestrogen. In our previous experiments, it was found that formononetin has a two-way regulatory effect on endothelial cells (ECs): low concentrations promote the proliferation of ECs and high concentrations have an inhibitory effect. To find a specific mechanism of action and provide a better clinical effect, we performed a structural transformation of formononetin and selected better medicinal properties for formononetin modifier J1 and J2 from a variety of modified constructs. The MTT assay measured the effects of drugs on human umbilical vein endothelial cell (HUVEC) activity. Scratch and transwell experiments validated the effects of the drugs on HUVEC migration and invasion. An in vivo assessment effect of the drugs on ovariectomized rats. Long-chain non-coding RNA for EWSAT1, which is abnormally highly expressed in HUVEC, was screened by gene chip, and the effect of the drug on its expression was detected by PCR after the drug was applied. The downstream factors and their pathways were analysed, and the changes in the protein levels after drug treatment were evaluated by Western blot. In conclusion, the mechanism of action of formononetin, J1 and J2 on ECs may be through EWSAT1-TRAF6 and its downstream pathways.

Dandelion Chloroform Extract Promotes Glucose Uptake via the AMPK/GLUT4 Pathway in L6 Cells.

The number of patients with type 2 diabetes mellitus (T2DM) is increasing rapidly worldwide. Glucose transporter 4 (GLUT4) is one of the main proteins that transport blood glucose into the cells and is a target in the treatment of T2DM. In this study, we investigated the mechanism of action of dandelion chloroform extract (DCE) on glucose uptake in L6 cells. The glucose consumption of L6 cell culture supernatant was measured by a glucose uptake assay kit, and the dynamic changes of intracellular GLUT4 and calcium (Ca2+) levels were monitored by laser scanning confocal microscopy in L6 cell lines stably expressing IRAP-mOrange. The GLUT4 fusion with the plasma membrane (PM) was traced via myc-GLUT4-mOrange. GLUT4 expression and AMP-activated protein kinase (AMPK), protein kinase B (PKB/Akt), protein kinase C (PKC), and phosphorylation levels were determined by performing western blotting. GLUT4 mRNA expression was detected by real-time PCR. DCE up-regulated GLUT4 expression, promoted GLUT4 translocation and fusion to the membrane eventually leading to glucose uptake, and induced AMPK phosphorylation in L6 cells. The AMPK inhibitory compound C significantly inhibited DCE-induced GLUT4 expression and translocation while no inhibitory effect was observed by the phosphatidylinositol 3-kinase (PI3K) inhibitor Wortmannin and PKC inhibitor Gö6983. These data suggested that DCE promoted GLUT4 expression and transport to the membrane through the AMPK signaling pathway, thereby stimulating GLUT4 fusion with PM to enhance glucose uptake in L6 cells. DCE-induced GLUT4 translocation was also found to be Ca2+-independent. Together, these findings indicate that DCE could be a new hypoglycemic agent for the treatment of T2DM.

18ß-Glycyrrhetinic-acid-mediated unfolded protein response induces autophagy and apoptosis in hepatocellular carcinoma.

18ß-Glycyrrhetinic acid (GA) is the active ingredient of the traditional Chinese medicine, Glycyrrhrzae Radix et Rhizoma. Here, we explored the effects of GA on hepatocellular carcinoma (HCC) in vitro and in vivo and the underlying molecular mechanisms. We confirmed that GA suppressed proliferation of various HCC cell lines. Treatment of GA caused G0/G1 arrest, apoptosis and autophagy in HCC cells. GA-induced apoptosis and autophagy were mainly due to the unfolded protein response. We compared the roles of the ATF4/CHOP and IRE1α/XBP1s UPR pathways, which were both induced by GA. The ATF4/CHOP cascade induced autophagy and was indispensable for the induction of apoptosis in GA-treated HCC cells. In contrast, the IRE1α/XBP1s cascade protected HCC cells from apoptosis in vitro and in vivo induced by GA. Despite this, activation of autophagy protected HCC cells from apoptosis induced by GA. We concluded that pharmacological inhibition of autophagy or IRE1α may be of benefit to enhance the antitumor activity of GA.

Study on diagnosis criteria of fire-heat syndrome based on receiver operating characteristic curve and principal component analysis.

OBJECTIVE: To establish the diagnostic quantitative criteria for fire-heat syndrome (FHS) of Chinese medicine (CM) based on the receiver operating characteristic (ROC) curve and principal component analysis (PCA). METHODS: The symptoms and signs of FHS cases and healthy subjects from Guangzhou, Henan and Hunan of China were collected through questionnaire, and the diagnostic quantitative score tables were established for the three regions, respectively, with the method of maximum likelihood analysis. The homogeneity test was then performed on the diagnostic score tables for the three regions with ROC curve, and the diagnostic efficiency of diagnostic score tables for the three regions was compared with the prospective test and retrospective test. The method of PCA was adopted to obtain the analysis matrix for classifying the tapes of FHS. RESULTS: Twenty-seven elements of FHS were confirmed through Chi-square test, and the diagnostic score tables for the three regions were established with the method of maximum likelihood analysis on the basis of the collected case data. According to the ROC curve test, the areas under ROC curve of Guangzhou diagnostic score table assessment with candidates in Guangzhou, Henan and Hunan were 0.998, 0.961 and 0.956, respectively. It showed that the diagnostic efficiency of Guangzhou diagnostic score tables was the highest one. With the prospective test, the area under ROC of Guangzhou diagnostic score table was 0.949, and more than any other diagnostic score table. By PCA, FHS was classified into excess fire and deficiency fire, and then classified into syndrome of flaring up of Heart (Xin) fire, syndrome of Lung (Fei)-Stomach (Wei) excess fire, syndrome of deficiency of Liver (Gan)-yin and Kidney (Shen)-yin, and syndrome of deficiency of Lung-yin from the view of viscera. In the retrospective test, the consistency with clinicians' diagnosis was 69.4%, and in the prospective test, it was 70.1%. CONCLUSIONS: The Guangzhou diagnostic score table could be used as the recommended criteria for the diagnosis of FHS. The classification of FHS was basically in conformity with the clinical situation.

Tongqiao Huoxue Decoction ameliorates learning and memory defects in rats with vascular dementia by up-regulating the Ca(2+)-CaMKII-CREB pathway.

The present study was aimed at determining the effects of Tongqiao Huoxue Decoction (TQHXD) on the Ca(2+)-CaMKII-CREB pathway and the memory and learning capacities of rats with vascular dementia (VD). The rat VD model was established by using an improved bilateral carotid artery ligation method. The Morris water maze experiment was used to evaluate the ethology of the VD rats following treatments with TQHXD at 3.01, 6.02, and 12.04 g·kg(-1) per day for 31 days. At the end of experiment, the hippocampus were harvested and analyzed. Western blotting and RT-PCR were used to measure the expression levels of calmodulin-binding protein kinase II(CaMKII), protein kinase A(PKA), cAMP-response element binding protein(CREB), and three N-methyl-D-aspartic acid receptor subunits (NR1, NR2A, and NR2B). Our results revealed that TQHXD could alleviate the loss of learning abilities and increase the memory capacity (P < 0.05 and P < 0.01 vs the model group, respectively). The treatment with 6.02 and 12.04 g·kg(-1) of TQHXD significantly up-regulated the Ca(2+)-CaMKII-CREB pathway in the hippocampus. In conclusion, TQHXD showed therapeutic effects on a bilateral carotid artery ligation-induced vascular dementia model, through the up-regulation of calcium signalling pathways.

Chondrogenesis of human bone marrow mesenchymal stromal cells in highly porous alginate-foams supplemented with chondroitin sulfate.

To overcome the limited intrinsic cartilage repair, autologous chondrocyte or bone-marrow-derived mesenchymal stromal cell (BM-MSC) was implanted into cartilage defects. For this purpose suitable biocompatible scaffolds are needed to provide cell retention, chondrogenesis and initial mechanical stability. The present study should indicate whether a recently developed highly porous alginate (Alg) foam scaffold supplemented with chondroitin sulfate (CS) allows the attachment, survival and chondrogenesis of BM-MSCs and articular chondrocytes. The foams were prepared using a freeze-drying method; some of them were supplemented with CS and subsequently characterized for porosity, biodegradation and mechanical profile. BM-MSCs were cultured for 1-2 weeks on the scaffold either under chondrogenic or maintenance conditions. Cell vitality assays, histology, glycosaminoglycan (sGAG) assay, and type II and I collagen immunolabelings were performed to monitor cell growth and extracellular matrix (ECM) synthesis in the scaffolds. Scaffolds had a high porosity ~93-95% with a mean pore sizes of 237±48 µm (Alg) and 197±61 µm (Alg/CS). Incorporation of CS increased mechanical strength of the foams providing gradually CS release over 7 days. Most of the cells survived in the scaffolds. BM-MSCs and articular chondrocytes formed rounded clusters within the scaffold pores. The BM-MSCs, irrespective of whether cultured under non/chondrogenic conditions and chondrocytes produced an ECM containing sGAGs, and types II and I collagen. Total collagen and sGAG contents were higher in differentiated BM-MSC cultures supplemented with CS than in CS-free foams after 14 days. The cell cluster formation induced by the scaffolds might stimulate chondrogenesis via initial intense cell-cell contacts.

Inhibition of proprotein convertase subtilisin/kexin type 9: a novel mechanism of berberine and 8-hydroxy dihydroberberine against hyperlipidemia.

OBJECTIVE: To investigate the effect and molecular mechanisms of different doses of 8-hydroxy dihydroberberine (Hdber) for the treatment of hyperlipidemia in rats. METHODS: A rat model of hyperlipidemia was established by feeding rats a high-fat diet for 4 weeks in 70 rats of 80 animals, and 10 rats were randomly selected as control group. The hyperlipidemic rats were then randomly divided into the following groups: a model group (MOD); a berberine group [BBR, 156 mg/(kg day)]; Hdber groups, which were treated with different doses of Hdber [78, 39 and 19.5 mg/(kg day)]; and a simvastatin group [SIM, 4 mg/(kg day)]. The corresponding therapy was administered to the rats of each treatment via gastric tubes. Normal animals were used as a control group. The blood levels of various lipids, including total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, free fatty acid (FFA), apolipoprotein AI(Apo-AI) and apolipoprotein B (Apo-B) were examined. The protein expressions of low-density lipoprotein receptor (LDL-R), sterol regulatory element-binding protein 2 (SREBP-2), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) and proprotein convertase subtilisin/kexin type 9 (PCSK-9) in liver tissues were determined by Western blot analysis. RESULTS: Compared with the control group of rats, the model group demonstrated a deteriorated blood lipid profile and exhibited increased expression levels of PCSK-9 protein in their liver tissues (P<0.01). In addition, the high-fat diet decreased the expression levels of LDL-R, SREBP-2 and HMGCR proteins in murine liver tissues. However, the addition of berberine or Hdber reversed the blood lipid profile changes (P<0.05 or P<0.01), decreased the expression levels of PCSK-9 proteins (P<0.01), and increased the expression levels of LDL-R proteins in the hyperlipidemic rats (P<0.01). These compounds did not significantly influence the expression levels of SREBP-2 and HMGCR proteins in the hyperlipidemic rats. CONCLUSIONS: Hdber is effective in the treatment of hyperlipidemia in rats. The therapeutic mechanisms of Hdber may be associated with increasing the expression of LDL-R protein and decreasing the expression of PCSK-9 protein in liver tissues.

[Effect of Kuanxiong aerosol on coronary heart disease angina patients: a multicenter randomized controlled clinical study].

OBJECTIVE: To evaluate the anginal attack-relieving efficacy and safety of Kuanxiong Aerosol (KA) in patients with coronary heart disease (CHD). METHODS: A total of 780 patients confirmatively diagnosed as CHD angina from November 2011 to December 2012 in 13 medical centers in the mainland area were assigned to 2 groups by blocked randomization, the treatment group (376 cases) and the control group (374 cases). When the angina attacked, patients in the treatment group received sublingual spray three times, 0.6 mL each time, while those in the control group sublingually dissolved Nitroglycerin Tablet (NT), 0.5 mg each tablet. The effective rate of angina relief, efficacy of electrocardiogram (ECG), and the incidence of adverse reactions were observed. RESULTS: The 3 min and 5 min remission rates of angina attack were 53.72% (202/376) and 94.41% (355/376) in the treatment group, and 47.86% (179/374) and 90.64% (339/374) in the control group. The 95% confidence interval (CI) of the difference between the 2 groups of 3 min and 5 min remission rates of angina attacks were [(-1.84%, 12.32%) and (-1.33%, 6.85%) respectively, P > 0.05]. The total improvement rates of ST-T changes in the treatment group and the control group after treatment were 74.07% and 73.13% respectively (P > 0.05). The adverse reaction rate was 9.31 (35/376 cases) in the treatment group and 22.46% (84/374 cases) in the control group (P < 0.01). CONCLUSION: KA was not inferior to NT in relieving anginal attacks and improving ischemic ECG changes, and had obviously less adverse reaction.

Molecular cloning and characterization of 5-enolpyruvylshikimate-3-phosphate synthase gene from Convolvulus arvensis L.

5-Enolpyruvylshikimate-3-phosphate synthase (EPSPS), the target enzyme for glyphosate inhibition, catalyzes an essential step in the shikimate pathway for aromatic amino acid biosynthesis. The full-length cDNA of 1,751 nucleotides (CaEPSPS, Genbank accession number: EU698030) from Convolvulus arvensis was cloned and characterized. The CaEPSPS encodes a polypeptide of 520 amino acids with a calculated molecular weight of 55.5 kDa and an isoelectric point of 7.05. The results of homology analysis revealed that CaEPSPS showed highly homologous with EPSPS proteins from other plant species. Tissue expression pattern analysis indicated that CaEPSPS was constitutively expressed in stems, leaves and roots, with lower expression in roots. CaEPSPS expression level could increase significantly with glyphosate treatment, and reached its maximum at 24 h after glyphosate application. We fused CaEPSPS to the CaMV 35S promoter and introduced the chimeric gene into Arabidopsis. The resultant expression of CaEPSPS in transgenic Arabidopsis plants exhibited enhanced tolerance to glyphosate in comparison with control.

Use of evidence-based pharmacotherapy for secondary prevention of coronary heart disease: a Chinese medicine hospital versus a general hospital.

OBJECTIVE: To determine differences in adherence to secondary prevention guidelines (pharmacological interventions) among coronary heart disease (CHD) patients between a Chinese medicine (CM) hospital and a general hospital in a Chinese city. METHODS: Medical records of 200 patients consecutively discharged from the CM hospital and the general hospital for CHD were reviewed to determine the proportions of eligible patients who received antiplatelet agents, ß-blockers, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and statins at discharge. The effects of patient characteristics and hospital type on the use of these medicines were estimated using logistic regression models. RESULTS: Patients discharged from the CM hospitals were older; more likely females; had greater history of hyperlipidemia, cerebrovascular diseases and less smoker (P<0.01 or P<0.05). They were less likely to receive coronary angiography and percutaneous coronary intervention, and had a longer length of stay than those discharged from the general hospital (P<0.01 or P<0.05). There were no significant differences in antiplatelet agents (96% vs. 100%, P=0.121) or statins (97.9% vs. 100%, P=0.149) use between the CM hospital and the general hospital. In multivariable analyses that adjusted for patient characteristics and hospital type, there was no significant difference in use of ß-blockers between the CM hospital and the general hospital. In contrast, patients discharged from the CM hospital were less likely to receive ACE inhibitors/ARBs compared with those discharged from the general hospital (odds ratio: 0.3, 95% confidence interval: 0.105-0.854). CONCLUSION: In this study, the CM hospital provides the same quality of care in CHD for prescribing evidence-based medications at discharge compared with another general hospital except for ACE inhibitors/ARBs use.

Effects of Chinese Fructus Mume formula and its separated prescription extract on insulin resistance in type 2 diabetic rats.

The effect of Fructus Mume formula and its separated prescription extract on insulin resistance in type 2 diabetic rats was investigated. The rat model of type 2 diabetes was established by feeding on a high-fat diet for 8 weeks and by subsequently intravenous injection of small doses of streptozotocin. Rats in treatment groups, including the Fructus Mume formula treatment group (FM), the cold property herbs of Fructus Mume formula treatment group (CFM), the warm property herbs of Fructus Mume formula treatment group (WFM), were administrated with Fructus Mume formula and its separated prescription extract by gavage, while the rats in diabetic model group (DM) and metformin group (MET) were given by gavage with normal saline and metformin correspondingly. The body weight before and after treatment was measured, and the oral glucose tolerance test (OGTT) and the insulin release test (IRT) were performed. The homeostasis model assessment-insulin resistance index (HOMA-IR) was calculated. The protein and mRNA expression levels of Insr, ß-arrestin-2, Irs-1 and Glut-4 in the liver, skeletal muscle and fat tissues were detected by using Western blotting and RT-PCR respectively. The results demonstrated that, as compared with DM group, OGTT, IRT (0 h, 1 h) levels and HOMR-IR in treatment groups were all reduced, meanwhile their protein and mRNA expression levels of Insr, Irs-1 and Glut-4 in the liver, skeletal muscle and fat tissues were obviously increased, and their protein and mRNA expression levels of ß-arrestin-2 in the liver and skeletal muscle tissues were also markedly increased. It was suggested that the Fructus Mume formula and its separated prescription extracts could effectively improve insulin resistance in type 2 diabetic rats, which might be related to the up-regulated expression of Insr, Irs-1 and Glut-4 in the liver, skeletal muscle and fat tissues, and ß-arrestin-2 in the liver and skeletal muscle tissues.

Periconceptional folic acid supplementation among women attending antenatal clinic in Anhui, China: data from a population-based cohort study.

OBJECTIVES: to examine the rate of periconceptional and optimal folic acid supplementation, and to characterise their patterns and determinants among antenatal women in central China. DESIGN: data from 4290 women in the Anhui Birth Defects and Child Development Cohort Study recruited between October 2008 and September 2009 were analysed. SETTING: seven Maternal and Child Health Centres of two cities (Hefei and Maanshan) in Anhui province of central China. PARTICIPANTS: women initiating prenatal care were included and asked to complete a structured questionnaire regarding folic acid supplementation. FINDINGS: sixty-eight per cent (2905/4290) of pregnant women reported taking folic acid supplementation periconceptionally (i.e. at some point before or during early pregnancy), and 32.8% (1405/4290) and 65.2% (2797/4290) had taken it before or during early pregnancy, respectively. However, only 16.1% (690/4290) used it optimally (i.e. regularly from four weeks before pregnancy throughout four weeks after pregnancy). Use of periconceptional folic acid was significantly associated with educational level, household income, registered residence, age, gestational age at recruitment, and planning of pregnancy. CONCLUSION: optimal folic acid supplementation was relatively low. IMPLICATIONS FOR PRACTICE: further efforts are needed to inform the population and promote the use of folic acid supplementation.