FTY720 and IMMH002, prodrugs for sphingosine-1-phosphate receptor 1 (S1P) agonists, show inadequate and inconsistent levels of phosphorylation in humans compared to that in rats. In this study, FTY720 or IMMH002 analogues (-) were designed and synthesized with modified head pieces to improve the biotransformation of the prodrugs to the active phosphorylated forms. Target compounds were synthesized a convergent route using the key and optically pure building block , which was first synthesized asymmetrically catalyzed amination. The phosphorylation rates of these analogues in rat or human blood were compared. The new methyl-substituted analogue compound showed higher phosphorylation rates in both rats and humans than the parent compound, whereas compound showed improvements in rats, but not in humans. In pharmacokinetics studies of rats, compounds and both had higher levels of phosphorylation than FTY720 and IMMH002. Thus, our study not only yielded new compounds with therapeutic potential, but also showed species differences between rats and humans in response to the structural modifications, which might be useful for predicting the biotransformation behavior and efficacy of this class of prodrugs in the clinic.

Objective:To explore the key genes and pathways that may play an important role in the pathogenesis of acne by bioinformatics analysis.Methods:GSE6475 and GSE53795 datasets were collected from GEO database, and 18 acne lesions tissues and 18 normal skin tissues were compared. David database was used to analyze the gene ontology (GO) and the key pathway (Kyoto Encyclopedia of genes and genomes, KEGG) of the differential genes, to establish the protein interaction network of the differential genes, and to obtain the most relevant key genes and important clusters.Results:A total of 314 up-regulated genes and 62 down-regulated genes were filtered from those GEO profiles. KEGG pathway analysis showed that these differential genes were mainly enriched in Staphylococcus aureus infection, osteoclast differentiation, pentose and glucuronate interconversions. In addition, 379 nodes and ten key genes (CXCL8, PTPRC, IL1B, ITGB2, CXCR4, ICAM1, CCR5, SELL, C3AR1 and PLEK) were screened out by protein interaction network.Conclusions:The key genes and pathways identified in this study may be new targets for intervention in the development of acne.

Objective Although heart transplantation (HTx) has become a standard therapy for end-stage heart diseases,experience with pediatric HTx is limited in China.In this article,we will try to provide the experience with indications,complications,perioperative management,immunosuppressive therapy,and survival for pediatric HTx based on our clinical work.Method This is a retrospective chart review of the pediatric patients undergoing HTx at Department of Cardiovascular Surgery of Union Hospital from September 2008 to December 2015.We summarized the indications,surgical variables,postoperative complications,and survival for these patients.Result Twenty-three pediatric patients presented for HTx at Union Hospital of Tongji Medical College,of whom 12 were male.The age at the time of transplantation ranged from 3 months to 18years (median 14 years).Patient weight ranged from 5.2 kg to 57.0 kg (median 36.0 kg).Pretransplant diagnosis included cardiomyopathy (16 cases),complex congenital heart disease (5cases) and tumors (2 cases).All recipients received ABO compatible donor hearts.Postoperative complications occurred in 14 patients,including cardiac dysfunction,arrhythmia,pulmonary infection,renal dysfunction,and rejection.Two of them experienced cardiac failure and required extracorporeal membrane oxygenation.The immunosuppression regimen was comprised of prednisone,a calcineurin inhibitor,and mycophenolate.All patients recovered with New York Heart Association (NYHA) Class Ⅰ Ⅱ cardiac function and were discharged.Only one patient suffered sudden death 19 months after transplantation.Conclusion Orthotopic HTx is a promising therapeutic option with satisfactory survival for the pediatric population in China with end-stage heart disease.

Culture of pharmaceutical plant is a comprehensive multi-disciplinary theory, which has a long history of application. In order to improve the quality of this course, some reformation schemes have been carried out, including stimulating enthusiasm for learning, refining the basic concepts and theories, promoting the case study, emphasis on latest achievements, enhancing exercise in laboratory and planting base, and guiding students to do scientific and technological innovation. Meanwhile, the authors point out some teaching problems of this course.
Education, Medical ; Humans ; Pharmacognosy ; education ; legislation & jurisprudence ; Plants, Medicinal ; growth & development

Effects of light quality and germplasm on the growth and effective ingredients of Dendrobium officinale germchit were studied. Under 8 light qualities (red, blue, yellow, green and three different red blue mix light), test-tube plantlets of different families (9 x 66, 17 x 30, 78 x 68) were used in the experiment to measure economical character and determine the content of chlorophyll, polysaccharides and total alkaloids. The results showed that light quality, germplasm and their interaction had a significant effect on the growth of D. officinale germchit. The maximal root length and height of seedling were obtained under red light, under blue light, the stem diameter was thickest and the content of total alkaloids were highest, the content of chlorophyll and polysaccharides of test-tube plantlets under red blue mix light were higher than that of other treatments. This work has laid a foundation for the high quality, low carbon and efficient production of D. officinale, and gives useful tips on production of high quality ingredients.
Alkaloids ; metabolism ; Breeding ; Chlorophyll ; metabolism ; Dendrobium ; genetics ; growth & development ; radiation effects ; Light ; Plant Roots ; genetics ; growth & development ; radiation effects ; Plant Stems ; genetics ; growth & development ; radiation effects ; Polysaccharides ; metabolism ; Seedlings ; genetics ; growth & development ; radiation effects

OBJECTIVETo find out the variation of 11 mental element contents in Dendrobium officinale with different germplasms and harvesting ages, the results can provide scientific basis for the quality evaluation and the breeding of D. officinale.

METHOD32 samples with 1-3 ages were collected from cultivated fields of Zhejiang and 11 samples were collected from markets. The 11 mental element contents of samples were determined by ICP-MS or AAS.

RESULTThe average contents of K, Ca, Mg, Mn, Zn, Cr, and Cu were 1,205.23, 766.82, 158.25, 31.06, 4.28, 8.28, and 0.97 mg x kg(-1), the contents of As, Hg, Pb, and Cd were all in limits except Cd content of one sample exceeded the standard limit 0.07 mg x kg(-1); germplasms and physiological ages impacted mental elements contents accumulation significantly.

CONCLUSIONThere were rich essential mental elements in D. officinale. D. officinale from Zhejiang province and medical materials from market were all safe; the breeding of D. officinale can increase the contents of essential mental elements and reduce contents of heavy mental elements; the effect of physiological age on metal elements contents was related to each element's physiological and biochemical function.

The monosacchride composition of polysacchrides in Dendrobium officinal of different germplasms, physiological ages and closely related species were determined by pre-column derivatization HPLC. The results showed that the absolute and relative volumes of all monosacchrides were significantly different between D. officinale and its closely related species, different germplasms and physiological ages of D. officinale. Absolute peak areas of mannose ranged from 0.854 x 10(7) to 10.340 x 10(7) in closely related species of D. officinale, ranged from 1.467 x 10(7) to 8.475 x 10(7) in different germplasms of D. officinale and were 4.411 x 10(7) (2.577 x 10(7)-6.516 x 10(7)), 5.528 x 10(7) (3.179 x 10(7)-8.475 x 10(7)) and 3.601 x 10(7) (1.467 x 10(7)-5.888 x 10(7)), respectively, in one to three physiological ages of D. officinale. The ratio of mannose to glucose peak areas (relative peak area) ranged from 0.976 to 16.599 in closely related species of D. officinale and from 2.679 to 7.831 in different germplasms of D. officinale. Only the relative peak areas of D. pendulum and D. primulinum were in the range of different germplasms of D. officinale in all tested samples. The results revealed the variation of monosacchride composition of polysacchrides in D. officinale. Monosacchride composition of D. officinale could be altered by breeding new varieties and controlling harvesting season. Most adulterants of D. officinale could be ruled out according to the relative peak areas of D. officinale, providing a basis for quality control and resources training of D. officinale.
Breeding ; methods ; Chromatography, High Pressure Liquid ; methods ; Dendrobium ; chemistry ; metabolism ; Glucose ; metabolism ; Mannose ; metabolism ; Monosaccharides ; metabolism ; Plant Extracts ; chemistry ; metabolism ; Plants, Medicinal ; chemistry ; Polysaccharides ; chemistry ; metabolism

To reveal the effects of harvesting stage on the functional constituents of four kinds of Hangbaiju and determine the best harvesting stage. Sixteen samples of Hualei, Taiju, Youju, Quanju were collected from Zhejiang Tongxiang. The content of total flavonoids were determined by UV spectrophotometry. Chlorogenic acid, lutelin-7-O-beta-D-glucoside and 3,5-O-discaffeoylquinc acid were analyzed by HPLC. The results showed that the effect of harvesting stage on the functional constituents of four kinds of Hangbaiju was significant. The contents of total flavonoids and chlorogenic acid reached maximum at the Hualei stage, and next was Taiju. The highest content of lutelin-7-O-beta-D-glucoside and 3,5-O-discaffeoylquinc acid was found in samples of Taiju. The yield of the four kinds of Hangbaiju increased obviously as the collection time deferred. Considering the functional constituents, yield and harvesting stage, the stage of Taiju is the best harvesting time.
Chlorogenic Acid ; analysis ; metabolism ; Chromatography, High Pressure Liquid ; Chrysanthemum ; chemistry ; growth & development ; metabolism ; Drugs, Chinese Herbal ; analysis ; metabolism ; Flavonoids ; analysis ; metabolism ; Glucosides ; analysis ; metabolism ; Time Factors

OBJECTIVETo provide the theoretical basis and applied technology for breeding superior species of Dendrobium officinale.

METHODThe peroxidase solution was used to test the pollen vigor in different flowering time and storage conditions. Cross, self and opening pollination were conducted in the green house, the subsidiary pollination by insects was carried out outdoors.

RESULTThe pollen of D. officinale was still in vigor when the flower faded. The pollen vigor was only 29.4% in the buds, 70.6% in the bloom day, and decreased to 31.9% a week later, it remained still 21.2% 20 days later under the condition of dry and 4 degrees C. The fructification rate was about 82.6% and 7.3%, respectively, when the cross and self pollination performed by hand in the whole flowering time, the rate was 0 in the green house and outdoors.

CONCLUSIONThe pollen of D. officinale was still in vigor during the whole flowering time, the fructification rate was 0 in the green house and outdoors resulted from the specific structure of flower. The wild resources of D. officinale were protected and germplasm was developed effectively through the artificial cross pollination.

OBJECTIVETo investigate the contents of 16 basic amino acid and find out the variation of them in Dendrobium officinale with different germplasms and physiological ages, and then provide scientific basis for the quality evaluation and the breeding of D. officinale.

METHODThirty-three samples with 1-3 ages were collected from cultivated fields of Zhejiang. The samples were acid hydrolyzed, and then 16 basic amino acid contents of samples were determined by amino acid analyzer.

RESULTThe average contents of 7 necessary amino acid were in 0.28 - 2.96 mg x g(-1), the average contents of other 9 basic amino acid were in 0.53 - 4.20 mg x g(-1). The contents of many amino acids were impacted by germplasms significantly, and contents of several amino acids were impacted by physiological ages significantly.

CONCLUSIONThere were rich basic amino acids in D. officinale. The breeding of D. officinale can increase the contents of essential amino acids and other basic amino acids. The relations among physiological age and amino acid contents were as follows: three years > two years > one year. The contents of Asp and Tyr have significantly negative correlation with magnesium, the content of Pro has significantly positive correlation with copper.