Biomedical subjects

Ying Zhang

Publications and source records attributed to Ying Zhang.

At least 361 records · Page 20Linked to original sources

PubMed2004

The preparation of insoluble fibroin films induced by degummed fibroin or fibroin microspheres.

Blending degummed fibroin (DF) or insoluble fibroin microspheres with concentrated fibroin solution, the insoluble films were obtained through drying the solution at 40-45 degrees C. The conformation of silk fibroin films was analyzed by infrared spectrum and X-ray diffractometry. The results demonstrated that beta-sheet conformation increased rapidly when the degummed silk or insoluble microspheres blended with fibroin, while the pure SF membrane was mainly composed of alpha/random coil conformation when the other conditions kept same. This suggested that fibroin microspheres and degummed fibroin could induce the formation of beta-sheet crystal and the insoluble films, without methanol after-treatment, could be obtained at approximately room temperature. Although the fibroin films blending with DF had many protuberances, the films containing fibroin microspheres had the smooth surface and could be used effectively in biotechnological materials and biomedical application.

Biocompatible Materials↗

PubMed2004

Anomeric specificity of D-[U-14C]glucose incorporation into glycogen in rat hemidiaphragms.

The anomeric specificity of D-[U-14C]glucose incorporation into glycogen in rat hemidiaphragms was investigated. For this purpose, the hemidiaphragms were preincubated for 30 min at 37 degrees C and then incubated for 5 min at the same temperature in the presence of alpha- or beta-D-[U-14C]glucose. The concentrations of D-glucose (5.6 or 8.8 mM) and insulin (0 or 10 mU/ml) were identical during the preincubation and incubation periods. The incubation medium was prepared in D2O/H2O (3:1, v/v) in order to delay the interconversion of the D-glucose anomers. In addition to glycogen labelling, the output of radioactive acidic metabolites was also measured. Insulin caused a preferential stimulation of glycogen labelling relative to glycolysis. Such was not the case in response to a rise in D-glucose concentration. At 5.6 mM D-glucose and whether in the presence or absence of insulin, both glycogen labelling and glycolysis were lower with alpha-D-glucose than with beta-D-glucose suggesting a higher rate of beta-D-glucose than alpha-D-glucose transport across the plasma membrane. A mirror image was found at 8.8 mM D-glucose, especially in the absence of insulin. At this close-to-physiological hexose concentration, insulin lowered the alpha/beta ratio for glycogen labelling. On the contrary, the rise in D-glucose concentration increased such a ratio. Since such a rise is probably little affected by any possible anomeric difference in D-glucose transport across the plasma membrane, the present results strongly suggest that the intracellular factors regulating net glycogen synthesis, as well as glycolytic flux, display obvious preference for alpha-D-glucose.

Animals↗

PubMed2004

Accurate mapping of mutations of pyrazinamide-resistant Mycobacterium tuberculosis strains with a scanning-frame oligonucleotide microarray.

The increasing emergence of drug-resistant Mycobacterium tuberculosis poses significant threat to the treatment of tuberculosis. Conventional susceptibility testing for the front-line tuberculosis drug pyrazinamide (PZA) is difficult, because of the requirement for acid pH for the drug to show activity. Resistance to PZA in M. tuberculosis is caused by mutations in the pncA gene, and detection of pncA mutations can be an indicator of PZA resistance. In this study, we examined the feasibility of a microarray-based approach exploiting short overlapping oligonucleotides (sliding-frame array) to rapidly detect pncA mutations (substitutions, deletions, and insertions) in multiple strains of PZA-resistant M. tuberculosis. The genetic mapping of these mutations is necessary to link the gene sequence to the protein function defined by mutant phenotype. Microarray analysis was performed in a blind manner using 57 isolates of M. tuberculosis for which the sequence of the pncA gene was previously determined. Our results showed that all mutations could be unambiguously detected, suggesting that microarray can be a routine and valuable tool for rapid identification of drug-resistant M. tuberculosis isolates. We expect that mutation mapping with a sliding-frame microarray will accelerate the molecular analysis of drug-resistant M. tuberculosis bacteria and the microorganism populations.

DNA, Bacterial↗

PubMed2004

Safety evaluation of a triterpenoid-rich extract from bamboo shavings.

Triterpenoids, which may have significant application to the development of natural medicines and functional foods as biological active components, are widely distributed throughout the plant kingdom. This paper evaluated the safety of a triterpenoid-rich extract of bamboo shavings (EBS) systematically. (i) Acute toxicity test: The oral maximum tolerated dose of EBS was more than 10 g/kg body weight both in rats and in mice, due to the absence of toxicity according to the criteria of acute toxic classifications. (ii) Mutagenicity test: It had no mutagenicity judged by negative experimental results of Ames test, mouse bone marrow cell micronucleus test and mouse sperm abnormality test. (iii) 30 days feeding study: No abnormal symptoms and clinical signs or deaths had been found in rats in each group during the test. No significant difference had been found in body weight, food consumption and food availability of rats in each test group (P>0.05). In addition, no significant differences were found in each hematology value, clinical chemistry value and organ/body weight ratio, either (P>0.05). No abnormality of any organ was found during histopathological examination. It can be concluded that the extract of bamboo shavings is of low toxicity and support the use of EBS for various foods.

Administration, Oral↗

PubMed2004

Crystal structure of a novel antifungal protein distinct with five disulfide bridges from Eucommia ulmoides Oliver at an atomic resolution.

EAFP2 is a novel antifungal protein isolated from the bark of the tree Eucommia ulmoides Oliver. It consists of 41 residues and is characterized with a five-disulfide motif and the inhibitory effects on the growth of both cell wall chitin-containing and chitin-free fungi. The crystal structure of EAFP2 at an atomic resolution of 0.84 A has been determined by using Shake-and-Bake direct methods with the program SnB. The phases obtained were of sufficient quality to permit the initial model built automatically and the structural refinement carried out using anisotropic displacement parameters resulted in a final crystallographic R factor of 6.8%. In the resulting structural model, all non-hydrogen protein atoms including an unusual pyroglutamyl acid residue at the N-terminal can fit to the articulated electron densities with one centre and more than 65% of the hydrogen atoms in the protein can be observed as individual peaks in the difference map. The general fold of EAFP2 is composed of a 3(10) helix (Cys3-Arg6), an alpha-helix (Ala27-Cys31) and a three-stranded antiparallel beta-sheet (Cys16-Ser18, Cys23-Ser25, and Cys35-Cys37) and cross-linked by five disulfide bridges. The tertiary structure of EAFP2 can be divided into two structural sectors, A and B. Sector A composed of residues 11-30 adopts a conformation similar to the chitin-binding domain in the hevein-like proteins and features a hydrophobic surface embraced a chitin-binding site (Tyr20, 22, 29, and Ser18). The distinct disulfide bridge Cys7-Cys37 connects the N-terminal ten residues with the C-terminal segment 35-41 to form the sector B, which features a cationic surface distributing all four positively charged residues, Arg6, 9, 36, and 40. Based on these structural features, the possible structural basis of the functional properties of EAFP2 is discussed.

Amino Acid Sequence↗

PubMed2004

Structure-activity comparison of YZ-069, a novel sigma ligand, and four analogs in receptor binding and behavioral studies.

Earlier studies show that antagonism of sigma receptors using high to moderate affinity compounds or antisense oligodeoxynucleotides targeting the sigma(1) subtype significantly attenuates the behavioral effects of cocaine in mice. In this study, the novel sigma receptor ligand YZ-069 [N-phenylpropyl-N'-(3,4-dichlorophenethyl)piperazine] and four analogs (representing nitrophenyl and methoxyphenyl derivatives) were evaluated in receptor binding and behavioral studies to further delineate structural features that convey favorable anticocaine actions. In receptor binding studies, all of the compounds had low nanomolar affinities for sigma(1) and sigma(2) receptors but only micromolar affinities for monoamine transporters. Consistent with the favorable affinities of the compounds for sigma receptors, they also significantly attenuated cocaine-induced convulsions in mice. The compounds with the 3,4-dichlorophenyl and methoxyphenyl substitutions provided better protection against cocaine-induced convulsions than the nitrophenyl derivative. This is consistent with the reduced lipophilicity of the nitro substitution, which would reduce its ability to cross the blood-brain barrier. The position of the substituent on the phenyl ring had no significant effect on binding affinity or behavioral protective actions. Together with earlier studies, the data suggest that favorable features of sigma receptor ligands with anticocaine actions include high affinity for brain sigma receptors, antagonistic actions at the receptor, and lipophilicity to facilitate crossing the blood-brain barrier.

Animals↗

PubMed2004

Conformational changes of the flavivirus E glycoprotein.

Dengue virus, a member of the Flaviviridae family, has a surface composed of 180 copies each of the envelope (E) glycoprotein and the membrane (M) protein. The crystal structure of an N-terminal fragment of E has been determined and compared with a previously described structure. The primary difference between these structures is a 10 degrees rotation about a hinge relating the fusion domain DII to domains DI and DIII. These two rigid body components were used for independent fitting of E into the cryo-electron microscopy maps of both immature and mature dengue viruses. The fitted E structures in these two particles showed a difference of 27 degrees between the two components. Comparison of the E structure in its postfusion state with that in the immature and mature virions shows a rotation approximately around the same hinge. Flexibility of E is apparently a functional requirement for assembly and infection of flaviviruses.

Amino Acid Sequence↗

PubMed2004

Gene silencing by nuclear orphan receptors.

Nuclear orphan receptors represent a large and diverse subgroup in the nuclear receptor superfamily. Although putative ligands for these orphan members remain to be identified, some of these receptors possess intrinsic activating, inhibitory, or dual regulatory functions in development, differentiation, homeostasis, and reproduction. In particular, gene-silencing events elicited by chicken ovalbumin upstream promoter-transcription factors (COUP-TFs); dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX-1); germ cell nuclear factor (GCNF); short heterodimer partner (SHP); and testicular receptors 2 and 4 (TR2 and TR4) are among the best characterized. These orphan receptors are critical in controlling basal activities or hormonal responsiveness of numerous target genes. They employ multiple and distinct mechanisms to mediate target gene repression. Complex cross-talk exists between these orphan receptors at their cognate DNA binding elements and an array of steroid?nonsteroid hormone receptors, other transcriptional activators, coactivators and corepressors, histone modification enzyme complexes, and components of basal transcriptional components. Therefore, perturbation induced by these orphan receptors at multiple levels, including DNA binding activities, receptor homo- or heterodimerization, recruitment of cofactor proteins, communication with general transcriptional machinery, and changes at histone acetylation status and chromatin structures, may contribute to silencing of target gene expression in a specific promoter or cell-type context. Moreover, the findings derived from gene-targeting studies have demonstrated the significance of these orphan receptors' function in physiologic settings. Thus, COUP-TFs, DAX-1, GCNF, SHP, and TR2 and 4 are known to be required for multiple physiologic and biologic functions, including neurogenesis and development of the heart and vascular system steroidogenesis and sex determination, gametogenesis and embryonic development, and cholesterol?lipid homeostasis.

Animals↗

PubMed2004

Alteration in N -acetylglucosaminyltransferase activities and glycan structure in tissue and bile glycoproteins from extrahepatic bile duct carcinoma.

The activities of three N -acetylglucosaminyltransferases (GnT)-III, IV and V, as well as the structural alterations of N-glycans on the glycoproteins in cancer tissues and bile specimens from 28 cases of extrahepatic bile duct carcinoma (EBDC) were compared with those from 18 cases of benign biliary duct diseases (BBDD). GnT activities were determined with fluorescence-labeled substrate using a HPLC method. It was found that GnT-III and GnT-V activities in EBDC were increased to 3.14 and 15.96 times respectively of the mean BBDD values, but GnT-IV remained unchanged. The activity of GnT-V was correlated with the grade of differentiation and TMN stage of EBDC. The up-regulation of GnT-III resulted in the increased bisecting-GlcNAc on the N-glycans of glycoproteins in cancer tissues and a 201 kDa bile glycoprotein when analyzed with HRP-labeled E(4)-PHA. The increased GnT-V activity led to the elevation of the beta1,6GlcNAc branch (or antennary number) on the N-glycans in cancer tissue glycoproteins and 201, 163, 122 kDa proteins in the bile as probed with HRP-labeled DSA. These findings suggest that the alteration in GnT activities may be involved in the malignant transformation and development of EBDC, resulting in the aberrant glycosylation of some tissue and bile proteins. The latter was expected to be used in the clinical diagnosis and prognosis evaluation in EBDC patients.

Adult↗

PubMed2004

Relations of the type and branch of surface N-glycans to cell adhesion, migration and integrin expressions.

The relations between the structure of cell surface N-glycans to cell behaviors were studied in H7721 human hepatocarcinoma cell line, which predominantly expressed complex-type N-glycans on the surface. 1-Deoxymannojirimycin (DMJ) and swaisonine (SW), the specific inhibitor of Golgi alpha-mannosidase II or I, were selected to block the processing of N-glycans at the steps of high mannose and hybrid type respectively. All-trans retinoic acid (ATRA) and antisense cDNA of N-acetylglucosaminyltransferase-V (GnT-V) were used to suppress the expression of GnT-V and decreased the GlcNAc beta1,6-branching or tri-/tetra-antennary structure of surface N-glycans. The structural alterations of N-glycans were verified by sequential lectin affinity chromatography of [3H] mannose-labeled glycans isolated from the cell surface. The cell adhesions to fibronectin (Fn) and human umbilical vein epithelial cell (HUVEC), as well as cell migration (including chemotaxis and invasion) were selected as the parameters of cell behaviors. It was found that cell adhesion and migration were significantly decreased in SW and DMJ treated cells, suggesting that complex type N-glycan is critical for the above cell behaviors. ATRA and antisense GnTV enhanced cell adhesion to Fn but reduce cell adhesion to HUVEC and cell migration. These results reveal that cell surface complex-type N-glycans with GlcNAc beta1,6 branch are more effective than those without this branch in the cell adhesion to HUVEC and cell migration, but N-glycan without GlcNAc beta1,6-branch is the better one in mediating the cell adhesion to Fn. The integrin alpha5beta1 (receptor of Fn) on cell surface was unchanged by DMJ and SW. In contrast, ATRA up regulated alpha5, but not beta1, and antisense GnT-V decreased both alpha5 and beta1. This findings suggest that both the structure of N-glycan and the expression of integrin on cell surface are two of the important factors in the determination of cell adhesion to Fn, a complex biological process.

1-Deoxynojirimycin↗

PubMed2004

Pre-eclampsia is associated with the failure of melanoma cell adhesion molecule (MCAM/CD146) expression by intermediate trophoblast.

The purpose of this study was to determine whether the expression of melanoma cell adhesion molecule (MCAM/CD146), like most other endothelial adhesion molecules, is reduced in the pregnancy disorder pre-eclampsia, and whether it is associated with the invasiveness of trophoblast. We used immunohistochemical approaches and analyzed 42 placentas from control and pre-eclamptic patients using an anti-CD146 monoclonal antibody. Our data show that in normal placentas, CD146 staining was specifically detected in intermediate trophoblasts that are most invasive and migratory, but not detected in noninvasive cytotrophoblasts or syncytiotrophoblasts. However in pre-eclampsia, CD146 was no longer present in the intermediate trophoblasts, although it was detectable in the blood vessels. At the same time, we tested CD31/PECAM-1, another endothelial adhesion molecule, and found its negative staining for all kinds of trophoblasts in both normal and pre-eclamptic placentas. The different staining patterns of CD146 in the normal and pre-eclamptic placentas provide the first evidence that in pre-eclampsia, intermediate trophoblasts fail to express CD146, implicating that CD146 plays an important role in trophoblast invasion.

Adult↗

PubMed2004

Extremely low bioavailability of magnesium lithospermate B, an active component from Salvia miltiorrhiza, in rat.

We assessed the bioavailability of magnesium lithospermate B (MLB), a main polyphenolic component of Salvia miltiorrhiza and a potent antioxidant having various pharmacological activities, to evaluate its action in vivo. The plasma concentrations of lithospermic acid B (LSB) showed a biexponential decrease after intravenous administration of MLB to rats at doses of 4 and 20 mg/kg. The values of area under the concentration-time curve (AUC; 87.8 +/- 10.9 and 1130 +/- 329 microg.min/mL), total body clearance (CL (tot); 55.52 +/- 7.07 and 23.51 +/- 5.98 mL/min/kg), and distribution volume at steady state (V (ss); 7.60 +/- 1.03 and 3.61 +/- 1.16 L/kg) suggested non-linear pharmacokinetics between the two doses. After oral administration of MLB at a high dose of 100 mg/kg, the mean AUC was barely 1.26 +/- 0.36 microg.min/mL. Absolute bioavailability of MLB was calculated to be 0.0002 from the AUC values after both intravenous dosing at 20 mg/kg and oral dosing at 100 mg/kg. The extremely low bioavailability was caused mainly by poor absorption from the rat gastrointestinal tract; about 65 % of the dose was retained in the tract even 4 h after oral administration, and most of the dose was retained even 20 min after infusion in an in situ jejunal loop experiment. Urinary and biliary excretion of LSB were only 0.70 % +/- 0.26 % and 5.10 % +/- 2.36 %, respectively, over a 30 h time period after intravenous injection despite the large CL (tot) and V (ss) values, and were much less (0.010 % +/- 0.001 % and 0.12 % +/- 0.04 %) after oral dosing. These findings suggest that extensive metabolism, including a first-pass effect, and wide distribution of LSB besides the poor absorption contributed significantly to the extremely low systemic bioavailability.

Administration, Oral↗

PubMed2004

Atypical apoptosis in L929 cells induced by evodiamine isolated from Evodia rutaecarpa.

Two alkaloids, evodiamine and rutaecarpine, isolated from the dried fruits of Evodia rutaecarpa Bentham were evaluated in vitro for antiproliferation activity on tumor cells versus human peripheral blood mononuclear cells (PBMC). Evodiamine had more potent cytotoxic effects on five tumor cell lines (human malignant melanoma A375-S2, human cervical cancer HeLa, human breast adenocarcinoma MCF7, human acute monocytic leukemia THP-1, murine fibrosarcoma L929) than rutaecarpine. Moreover, evodiamine did not affect PBMC viability for a 36 h culture period. Although apoptotic bodies were observed in evodiamine-treated L929 cells stained with Hoechst 33258, DNA fragmentation as a hallmark of apoptosis was not found. Caspases were involved in the protection of L929 cells against cell death. Evodiamine initiated atypical apoptosis in L929 cells by cycle arrest at the G0/G1 phase.

Adenocarcinoma↗

PubMed2004

Associations of postmenopausal hormone therapy with markers of hemostasis and inflammation and lipid profiles in diabetic and nondiabetic american Indian women: the strong heart study.

OBJECTIVES: To examine the associations of postmenopausal hormone therapy (PHT) with indicators of hemostasis and inflammation and with lipid profiles in American Indian women and to determine if diabetes modifies these associations. METHODS: This report is a cross-sectional analysis of data from 1446 postmenopausal women who were free from cardiovascular disease (CVD) at the second Strong Heart Study examination (1993-1995). Diabetes was diagnosed by WHO criteria. Postmenopausal hormone use was ascertained by review of the medications brought to the examination or by medical record review. Lipoproteins, plasminogen activator inhibitor type 1 (PAI-1), fibrinogen, and C-reactive protein (CRP) were measured in fasting plasma samples. RESULTS: Among nondiabetic women, current PHT users had lower mean fibrinogen, PAI1, and low-density lipoprotein cholesterol (LDLC) levels than those in never users (38.4 mg/dl, 8.68 ng/ml, and 14.16 mg/dl lower, respectively) but higher CRP and triglyceride levels (1.53 mg/l and 31.43 mg/dl higher, respectively). Multivariate adjustment did not alter any of these associations. In diabetic women, current PHT use was associated only with lower PAI-1 (5.48 ng/ml lower) and higher high-density lipoprotein cholesterol (HDLC) levels (3.33 mg/dl higher) compared with never users. CONCLUSIONS: In American Indian women without diabetes, PHT was associated with lower levels of hemostatic markers but higher levels of an inflammatory marker. Associations were less marked in women with diabetes. The relation of PHT with lipid profiles also differed in nondiabetic and diabetic women. These data provide an additional rationale for considering diabetes status when deciding whether or not to use PHT.

Aged↗

PubMed2004

Influence of trace amount of calponin on smooth muscle myosin in different states.

Calponin (CaP), a thin filament-associated protein, is thought to be involved in modulating smooth muscle contractile activity, but the role and mechanism keep unknown. In this study, trace amount of calponin (TAC) was found to obviously influence myosin in different states in Ca(2+)-independent manner, suggesting a high efficient interaction between TAC and myosin. In this assay, the lowest ratio of CaP vs. myosin was 1:10,000, with the concentration of CaP 10,000-fold lower than that used previously. Myosin phosphorylation, myosin Mg(2+)-ATPase activity and protein binding activity were detected to determine the effects of TAC on the myosin in different states. The amount of precipitated myosin that bound to TAC was used as the index to determine the interaction between myosin and TAC in binding assay. Our data showed that in the absence of actin, TAC significantly increased the precipitation of unphosphorylated myosin, Ca(2+)-dependently or independently phosphorylated myosin by MLCK, and stimulated the Mg(2+)-ATPase activities of these myosins slightly but significantly. However, no obvious change of precipitation of myosin phosphorylated by PKA was observed, indicating the relatively selective effect of TAC. In the presence of actin, the increase of myosin precipitations was abolished, and no obvious change of actin precipitations and actin-activated myosin Mg(2+)-ATPase activities were observed implicating the high efficiency of TAC on myosin being present in the absence of actin. Although we can not give conclusive comments to our results, we propose that the high efficiency of TAC-myosin interaction is present when actin is dissociated from myosin, even if CaP/myosin ratio is very low; this high efficient interaction can be abolished by actin. However, why and how TAC can possess such a high efficiency to influence myosin and how the physiological significance of the high efficiency of TAC is in regulating the interaction between myosin and actin remain to be investigated.

Actins↗

PubMed2004

Anaerobic incubation conditions enhance pyrazinamide activity against Mycobacterium tuberculosis.

Pyrazinamide (PZA) is an unconventional front line tuberculosis drug characterized by high in vivo sterilizing activity, but poor in vitro activity. This disparity in PZA activity may reflect differences between the in vivo tissue environment and in vitro culture conditions. This study examined the effect of anaerobic conditions, which exist in granulomatous lesions in vivo, on PZA activity in vitro. Low oxygen enhanced the activity of PZA against Mycobacterium tuberculosis, with anaerobic conditions resulting in greater enhancement than microaerobic conditions. ATPase and respiratory chain enzyme inhibitors enhanced PZA activity under normal atmospheric conditions, but not under anaerobic conditions. Furthermore, the inhibitors did not enhance isoniazid or rifampicin activity. Nitrate as an alternative electron acceptor antagonized PZA activity under anaerobic conditions. These findings provide further support for a proposed mechanism of action of PZA in which the active form of PZA (pyrazinoic acid) depletes the membrane energy reserve. They also provide another explanation for the higher sterilizing activity of PZA within in vivo lesions with low oxygen than under in vitro drug susceptibility testing conditions with ambient oxygen.

Adenosine Triphosphatases↗

PubMed2004

Magnesium lithospermate B is excreted rapidly into rat bile mostly as methylated metabolites, which are potent antioxidants.

To elucidate the in vivo pharmacological activities of magnesium lithospermate B (MLB), an active constituent of Radix Salviae Miltiorrhizae, in the rat, its metabolic fate both in vivo and in vitro was investigated. High-performance liquid chromatography revealed that four major metabolites with lower polarity were excreted into bile after intravenous and oral administration of MLB. The metabolites present in combined samples of bile from rats after intravenous injection were isolated and purified by column chromatography and identified as four meta-O-methylated products, namely 3-monomethyl- (M1), 3,3"'-dimethyl- (M2), 3,3"-dimethyl-, and 3,3",3"'-trimethyl-lithospermic acid B according to their spectroscopic characteristics ((1)H, (13)C NMR, (1)H-(1)H correlation spectroscopy, (1)H-detected multiple quantum coherence, and heteronuclear multiple bond coherence combined with positive ion fast atom bombardment-mass spectroscopy). After administration of MLB at an intravenous dose of 4 mg/kg or an oral dose of 100 mg/kg, the total biliary recovery of the four metabolites after 30 h reached 95.5 +/- 2.4% (with approximately 90% recovered within 2 h) or 5.5 +/- 0.7%, respectively. The metabolic pathway was proposed to involve sequential formation of the four methylated metabolites. Incubation of MLB, M1, M2, or M4 in rat hepatic cytosol in the presence of S-adenosyl-l-methionine demonstrated the formation of all four metabolites, which indicated that the enzyme responsible for the biotransformation is catechol O-methyltransferase. MLB and its main metabolites M1 and M2 showed potent 1,1-diphenyl-2-picrylhydrazyl radical-scavenging activities, the activity of M1 being stronger than those of caffeic acid (the monomer form of MLB) and alpha-tocopherol (a representative antioxidant) but weaker than that of MLB. The rapid and high biliary excretion levels of these metabolites suggested that they could undergo enterohepatic circulation in rats and that they might thereby be largely responsible for the pharmacological effects of MLB.

Administration, Oral↗

PubMed2004

Vaccine potential of the Neisseria meningitidis 2086 lipoprotein.

A novel antigen that induces cross-reactive bactericidal antibodies against a number of Neisseria meningitidis strains is described. This antigen, a approximately 28-kDa lipoprotein called LP2086, was first observed within a complex mixture of soluble outer membrane proteins (sOMPs) following a series of fractionation, protein purification, and proteomics steps. Approximately 95 different neisserial isolates tested positive by Western blotting and PCR screening methods for the presence of the protein and the gene encoding LP2086. The strains tested included isolates of N. meningitidis serogroups A, B, C, W135, and Y, Neisseria gonorrhoeae, and Neisseria lactamica. To better understand the microheterogeneity of this protein, the 2086 genes from 63 neisserial isolates were sequenced. Two different subfamilies of LP2086 were identified based on deduced amino acid sequence homology. A high degree of amino acid sequence similarity exists within each 2086 subfamily. The highest degree of genetic diversity was seen between the two subfamilies which share approximately 60 to 75% homology at the nucleic acid level. Flow cytometry (fluorescence-activated cell sorting) analyses and electron microscopy indicated that the LP2086 is localized on the outer surface of N. meningitidis. Antiserum produced against a single protein variant was capable of eliciting bactericidal activity against strains expressing different serosubtype antigens. Combining one recombinant lipidated 2086 (rLP2086) variant from each subfamily with two rPorA variants elicited bactericidal activity against all strains tested. The rLP2086 family of antigens are candidates worthy of further vaccine development.

Amino Acid Sequence↗