The asialoglycoprotein receptor (ASGPR) was used to mediate drug carrier for hepatic targeted drug delivery, this article showed the enzyme-catalyzed esterification of galactose and vinyl stearate and a kind of ASGPR ligand-targeted which was used to insert the surface of liposome has been synthesized. The structure of product has been confirmed by TLC, ESI-MS and 1H NMR. The factors of types and quantity of enzyme, organic solvents, molar ratio of substrate, temperature and time of reaction have been studied. Results showed when using acetone as reaction medium, the quantity of Novozym 435 immobilized lipase was 30 mg mL(-1), molar ratio of galactose to vinyl stearate was 1:5, and reacted at 60 degrees C for 12 h, the transformation of vinyl stearate reached more than 70%. This study provides a novel and efficient route to the synthesis of ligand-targeted modifier.

Objective Systematic evaluation of cerebrolysin in the treatment of neonatal hypoxic -ischemic encephalopathy.Methods Computer search Cochrane Library, EMBase, PubMed, Chinese Journal Full-text Database (CNKI), Chinese Biomedical Literature Database (CBM), Wanfang Database ( each database retrieval time from its creation to May 2016 ) About cerebrolysin Randomized controlled clinical trial of neonatal hypoxic -ischemic encephalopathy.According to the inclusion and exclusion criteria of the literature, the methodological quality of the included research was evaluated and the data were extracted.Metadata was analyzed by RevMan 5.3 software.Results A total of 41 RCT patients were enrolled, with a total of 3695 patients, the experimental group was 1932 cases, the control group was 1763 cases.Meta analysis showed, the efficacy of cerebrolysin in the treatment of neonatal hypoxic-ischemic encephalopathy was significantly higher than that in the control group [OR=3.85, 95% CI (3.15,4.70), P<0.000001], for the impact of clinical symptoms, the number of primitive reflexes of neonatal hypoxic-ischemic encephalopathy in the treatment group was significantly higher than that in the control group [MD=-1.22, 95% CI ( -2.06,-0.38), P=0.004], muscle tension recovery days[MD=-1.69, 95% CI ( -1.80,-1.58), P<0.00001], conscious state recovery days[MD=-1.32, 95% CI ( -2.25,-0.40), P=0.005], seizure recovery days [MD=-2.36, 95% CI ( -3.70, -1.03), P =0.0005], and other indicators were shorter than the control group, the difference between the experimental group and the control group was statistically significant.Conclusion Cerebrolysin havean effective in treating HIE.

ObjectiveTo explore the relationship between flash visual evoked potentials (fVEP) and intracranial pressure (ICP), and the effect of fVEP on monitoring ICP treatment.MethodsICPs of 37 patients with large area cerebral infarction and intracranial hypertension were measured before and at 10 min, 20 min, 30 min, 40 min, 50 min and 60 min after mannitol treatment.ResultsThe mannitol effect to cure the large area cerebral was not well.ConclusionfVEP can monitor ICP exactly and harmless, and has importance value to instruct therapy of ICP in clinic.

Cerebrolysin is an aqueous mixture of amino acids extracted from porcine brain, and mainly composed of 85% free amino acids and 15%small peptides. Cerebrolysin increase the metabolism of amino acids and glucose transport in the brain, improve the anti-anoxia ability of cells, and to enhance the brain's resistance to various types of malignant stimulation like stress and damage. Cerebrolysin can also promote synapse formation, induce neuronal differentiation, and help reverse brain injury. Because of its efficacy and safety, cerebrolysin has been widely used in the pediatric clinical practice, and primarily to treat neonatal hypoxic ischemic encephalopathy, childcerebral palsy, hyperactivity disorder, speech communication disorders, etc.The clinical symptoms were improved to some extent after the treatment of cerebrolysin. The recovery of consciousness, enhancement of comprehensionand memory, and improvement of the extremity motor function were observed. The treatment of cerebrolysincan not only enhance the cure rate, but also reduce the incidence of sequelae. This paper systematically summarized the clinical application of cerebrolysin in the pediatric population and relevant preclinical studies, to provide more guidance for clinical application of cerebrolysin in the treatment of pediatric diseases.

The asialoglycoprotein receptor (ASGPR) was used to mediate drug carrier for hepatic targeted drug delivery, this article showed the enzyme-catalyzed esterification of galactose and vinyl stearate and a kind of ASGPR ligand-targeted which was used to insert the surface of liposome has been synthesized. The structure of product has been confirmed by TLC, ESI-MS and 1H NMR. The factors of types and quantity of enzyme, organic solvents, molar ratio of substrate, temperature and time of reaction have been studied. Results showed when using acetone as reaction medium, the quantity of Novozym 435 immobilized lipase was 30 mg mL(-1), molar ratio of galactose to vinyl stearate was 1:5, and reacted at 60 degrees C for 12 h, the transformation of vinyl stearate reached more than 70%. This study provides a novel and efficient route to the synthesis of ligand-targeted modifier.
Acetone ; chemistry ; Asialoglycoprotein Receptor ; chemical synthesis ; Catalysis ; Esterification ; Galactose ; chemistry ; Ligands ; Lipase ; chemistry ; Stearates ; chemistry ; Temperature ; Vinyl Compounds ; chemistry

OBJECTIVETo study the effect of pseudolaric acid B (PLAB) on cell proliferation and cycle of human prostate carcinoma DU-145 cells. method: Its inhibitory effect on the cell growth was measured by MTT method. Characteristics of cell death were determined by Hoechest 33342 staining. The cell cycle was detected by flow cytometry. The expressions of cyclin B1, cyclin D1 and CDK1 were detected by Real time-PCR and Western blot, respectively.

RESULTPLAB notably inhibited DU-145 cell growth in a dose- and time dependent manner (P < 0.05). Its IC50 values of PLAB for DU-145 cells for 24, 48 and 72 h were 4.53, 2.39 and 2.08 micromol x L(-1), respectively. Having been treated with 5 micromol x L(-1) PLAB for 24 h, the cells showed such apoptosis characteristics as nuclei chromatin condensation and apoptotic body. With the increase in PLAB concentration, the proportion of G2/M phase cells strikingly increased in a dose- and time dependent manner (P < 0.05), meanwhile cyclin B1 and CDK1 showed over-expressions (P < 0.05), and the cyclin D1 showed under-expression (P < 0.05).

CONCLUSIONPLAB can inhibit the growth of DU-145 cells and induce the cell cycle G2/M arrest, accompanied with the over-expression of cyclin B1 and CDK1, which may be related with its regulation cycle-associated protein degradation.

Apoptosis ; drug effects ; Cell Cycle Checkpoints ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Diterpenes ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Male ; Prostatic Neoplasms ; drug therapy ; physiopathology

Angong Niuhuang Pills(AGNHP) are effective in clearing heat, removing the toxin, and eliminating phlegm for resuscitation. Clinically, it is widely used to treat various diseases such as febrile convulsion due to heat attacking pericardium, but its therapeutic effects on heart failure(HF) have not been well recognized. In this study, the profiles of differential metabolites regulated by AGNHP were identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). The underlying mechanism of AGNHP against HF was illustrated based on the integrated analysis of pharmacological data and metabolic molecular network. The HF model was induced by isoproterenol in mice. After oral administration of AGNHP for one week, cardiac functions in HF mice were evaluated by echocardiography, and serum samples of mice were collected for metabolomics analysis. Eight differential metabolites of AGNHP against HF were screened out through partial least square discriminant analysis(PLS-DA) and input into MetaboAnalyst for the analysis of metabolic pathways. Moreover, the critical metabolic pathways regulated by AGNHP were enriched according to the potential targets of major compounds in AGNHP. After AGNHP treatment, the recovered index of relative content of some metabolites underwent cross-scale fusion analysis with therapeutic efficacy data, followed by "compound-reaction-enzyme-gene" network analysis. It is inferred that the anti-HF effects of AGNHP may be attributed to the metabolism of arachidonic acid, amino acid, glycerophospholipid, and linoleic acid. The cross-scale polypharmacological analysis method developed in this study provides a new method to interpret scientific principles of AGNHP against HF with modern technologies.
Animals ; Biomarkers ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Heart Failure/drug therapy* ; Metabolomics ; Mice

Objective To study the single nucleotide polymorphisms (SNPs)that predict a patient's risk of grade 2-3 paclitaxel-induced peripheral sensory neuropathy (PSN) in Chinese Han populations.Methods Totally 216 patients received paclitaxel in Peking Union Medical College Hospital from May 2014 to December 2016 were enrolled.DNA was isolated from peripheral blood.Genotyping for eight candidate SNPs was performed on Sequenom-MassARRARYiPLEX platform.Patients were followed up and PSN was assessed by trained physicians according to National Cancer Institute-Common Terminology Criteria for Adverse Events v4.03.Results A total of 209 patients entered the final analysis.Among the candidate SNPs,only rs4141404:A>C(LIMK2) was significantly associated with grade 2/3 PSN (OR:4.32,95%CI:2.37-7.89,P<0.0001).In multivariate logistic regression analysis,both rs4141404:A>C(LIMK2) and history of receiving platinum compound (OR:2.70,95%CI:1.32-5.51,P=0.007) were associated with grade 2/3 PSN.Conclusion rs4141404:A>C(LIMK2) may be the markers of risk of grade 2/3 PSN.