Biomedical subjects

Li-Ming Yang

Publications and source records attributed to Li-Ming Yang.

18 recordsLinked to original sources

PubMed2007

Design of sandwichlike complexes based on the planar tetracoordinate carbon unit CAl4(2-).

Ever being a large curiosity, a series of simple "planar tetracoordinate carbon (ptC)" molecules have been recently characterized by experiments. Incorporation of such exotic ptC units into the assembled molecular materials, which will bridge the isolated clusters in molecular beams and the potential solid materials, is very challenging. In this paper, we described the first attempt on how to assemble the fewest-number ptC unit CAl42- into molecular materials in sandwich forms on the basis of the density functional theory calculations on a series of model compounds [D(CAl4)M]q- as well as the saturated compounds [D(CAl4)Mn] ((D = CAl42-, Cp-(C5H5-); M = Li, Na, K, Be, Mg, Ca). For M = Li, Be, Mg, and Ca, the ptC unit CAl42- can only be assembled in our newly proposed "heterodecked sandwich" scheme (e.g., [Cp(CAl4)M]q- (M = Li, Na, K, q = 2; M = Be, Mg, Ca, q = 1)) so as to avoid cluster fusion. For M = Na and K, the ptC unit CAl42- can be assembled in both the traditional "homodecked sandwich" [(CAl4)2M]q- (M = Li, Na, K, q = 3; M = Be, Mg, Ca, q = 2) and the novel heterodecked sandwich schemes. Moreover, the counterions were found to have an important role in determining the type of the ground structures for the homodecked sandwich. Various assembled species in extended frameworks were designed. Notably, among all the designed sandwich species, the ptC unit CAl42- generally prefers to interact with the partner deck at the side (Al-Al bond) or corner (Al atom) site. This has not been reported in the sandwich complexes on the basis of the known decks such as Cp-, P5-, N42-, and Al42-, for which only the traditional face-face interaction type was considered. Our results for the first time showed that the ptC unit CAl42- can act as a new type of "superatom". The present results are expected to enrich the flat carbon chemistry, superatom chemistry, metallocenes, and combinational chemistry.

Journal Article↗

PubMed2007

Microbial metabolism of steviol and steviol-16alpha,17-epoxide.

Steviol (2) possesses a blood glucose-lowering property. In order to produce potentially more- or less-active, toxic, or inactive metabolites compared to steviol (2), its microbial metabolism was investigated. Incubation of 2 with the microorganisms Bacillus megaterium ATCC 14581, Mucor recurvatus MR 36, and Aspergillus niger BCRC 32720 yielded one new metabolite, ent-7alpha,11beta,13-trihydroxykaur-16-en-19-oic acid (7), together with four known related biotransformation products, ent-7alpha,13-dihydroxykaur-16-en-19-oic acid (3), ent-13-hydroxykaur-16-en-19-alpha-d-glucopyranosyl ester (4), ent-13,16beta,17-trihydroxykauran-19-oic acid (5), and ent-13-hydroxy-7-ketokaur-16-en-19-oic acid (6). The preliminary testing of antihyperglycemic effects showed that 5 was more potent than the parent compound (2). Thus, the microbial metabolism of steviol-16alpha,17-epoxide (8) with M. recurvatus MR 36 was continued to produce higher amounts of 5 for future study of its action mechanism. Preparative-scale fermentation of 8 yielded 5, ent-11alpha,13,16alpha,17-tetrahydroxykauran-19-oic acid (10), ent-1beta,17-dihydroxy-16-ketobeyeran-19-oic acid (11), and ent-7alpha,17-dihydroxy-16-ketobeyeran-19-oic acid (13), together with three new metabolites: ent-13,16beta-dihydroxykauran-17-acetoxy-19-oic acid (9), ent-11beta,13-dihydroxy-16beta,17-epoxykauran-19-oic acid (12), and ent-11beta,13,16beta,17-tetrahydroxykauran-19-oic acid (14). The structures of the compounds were fully elucidated using 1D and 2D NMR spectroscopic techniques, as well as HRFABMS. In addition, a GRE (glucocorticoid responsive element)-mediated luciferase reporter assay was used to initially screen the compounds 3-5, and 7 as glucocorticoid agonists. Compounds 4, 5 and 7 showed significant effects.

Aspergillus niger↗

PubMed2007

Sandwich-like compounds based on the all-metal aromatic unit Al(4)2- and the main-group metals M (M=Li, Na, K, Be, Mg, Ca).

Inspired by the pioneering experimental characterisation of the all-metal aromatic unit Al(4)2- in the bimetallic molecules MAl4- (M=Li, Na, Cu) and by the very recent theoretical design of sandwich-type transition-metal complexes [Al4MAl4]q- (q=0-2; M=Ti, V, Cr, Zr, Nb, Mo, Hf, Ta, W), we used density functional theory (DFT) calculations (B3LYP/6-311+G(d) to design a series of novel non-transition-metal sandwich complexes based on the all-metal aromatic unit Al4(2-) and the main-group metals M (M=Li, Na, K, Be, Mg, Ca). The traditional homo-decked sandwich compounds [Al4MAl4]q- (without counterions) and (nM)q+[Al4MAl4]q- (with counterions M) (q=2-3, M=Li, Na, K, Be, Mg, Ca), although some of them are truly energy minima, have a much higher energy than many fused isomers. We thus concluded that it seems unlikely for Al4(2-) to sandwich the main-group metal atoms in the homo-decked sandwich form. Alternatively, we proposed a new type of sandwich complex, namely hetero-decked sandwich compounds [CpMAl4]q-, that are the ground-state structures for each M both with and without counterions. It was shown that with the rigid Cp- partner, the all-metal aromatic unit Al(4)2- might indeed act as a "superatom". These new types of all-metal aromatic unit-based sandwich complexes await future experimental verification.

Journal Article↗

PubMed2006

Biotransformation of gallic acid by Beauveria sulfurescens ATCC 7159.

Preparative-scale fermentation of gallic acid (3,4,5-trihydroxybenzoic acid) (1) with Beauveria sulfurescens ATCC 7159 gave two new glucosidated compounds, 4-(3,4-dihydroxy-6-hydroxymethyl-5-methoxy-tetrahydro-pyran-2-yloxy)-3-hydroxy-5-methoxy-benzoic acid (4), 3-hydroxy-4,5-dimethoxy-benzoic acid 3,4-dihydroxy-6-hydroxymethyl-5-methoxy-tetrahydro-pyran-2-yl ester (7), along with four known compounds, 3-O-methylgallic acid (2), 4-O-methylgallic acid (3), 3,4-O-dimethylgallic acid (5), and 3,5-O-dimethylgallic acid (6). The new metabolite genistein 7-O-beta-D-4''-O-methyl-glucopyranoside (8) was also obtained as a byproduct due to the use of soybean meal in the fermentation medium. The structural elucidation of the metabolites was based primarily on 1D-, 2D-NMR, and HRFABMS analyses. Among these compounds, 2, 3, and 5 are metabolites of gallic acid in mammals. This result demonstrated that microbial culture parallels mammalian metabolism; therefore, B. sulfurescens might be a useful tool for generating mammalian metabolites of related analogs of gallic acid (1) for complete structural identification and for further use in investigating pharmacological and toxicological properties in this series of compounds. In addition, a GRE (glucocorticoid response element)-mediated luciferase reporter gene assay was used to initially screen for the biological activity of the 6 compounds, 2-6 and 8, along with 1 and its chemical O-methylated derivatives 9-13. Among the 12 compounds tested, 11-13 were found to be significant, but less active than the reference compounds of methylprednisolone and dexamethasone.

Beauveria↗

PubMed2006

Selective COX-2 inhibitors. Part 1: synthesis and biological evaluation of phenylazobenzenesulfonamides.

A series of phenylazobenzenesulfonamide derivatives were designed and synthesized for the evaluation as selective cyclooxygenase-2 (COX-2) inhibitors in a cellular assay using human whole blood (HWB) and an enzymatic assay using purified ovine enzymes. Extensive structure-activity relationships (SAR) were studied within this series, and several of selective COX-2 inhibitors have been identified. Among them, compound 8, 4-(4-amino-2-methylsulfanyl-phenylazo)benzenesulfonamide, showed a potent inhibitory activity to the cyclooxygenase enzymes (IC(50)'s for COX-1: 23.28 microM; COX-2: 2.04 microM), being active but less COX-2 selective than celecoxib.

Azo Compounds↗

PubMed2006

Monosilicon-substituted cyanoacetylene: a computational study.

A detailed theoretical investigation of the [H,Si,C(2),N] potential energy surfaces including 28 minimum isomers and 65 interconversion transition states is reported at the Gaussian-3//B3LYP/6-31G(d) level. Generally, the triplet species lie energetically higher than the singlet ones. The former three low-lying isomers are linear HCCNSi 1 (0.00 kcal/mol), branched SiC(H)CN 12 (7.09 kcal/mol), and bent HNCCSi 7 (14.22 kcal/mol), which are separated by rather high barriers from each other and are kinetically very stable with the least conversion barriers of 32.6-70.5 kcal/mol. Two energetically high-lying isomers HCNCSi 3 (42.99 kcal/mol) and SiC(H)NC 13 (36.05 kcal/mol) are also kinetically stable with a barrier of 49.19 and 21.42 kcal/mol, respectively. Additionally, five high-lying isomers, that is, three chainlike isomers, HCCSiN 2 (55.17), HCSiNC 6 (47.80), HSiNCC 11 (78.83), and one three-membered ring isomer HN-cSiCC 19 (51.21), and one four-membered ring isomer cSiCN(H)C 27 (50.6 kcal/mol), are predicted to each have lower conversion barriers of 12-18 kcal/mol and can be considered as meta-stable species. All of the predicted 10 isomers could exist as stable or meta-stable intermediates under suitable conditions. Finally, the structural and bonding analysis indicate that the [H,Si,C(2),N] molecule contains various properties that are of chemical interest (e.g., silylene, SiC triple bonding, and conjugate SiN triple bonding and CC triple bonding, charge-transfer specie, planar aromatic specie, cumulate double bonding). This is the first detailed theoretical study on the potential energy surfaces of the series of hydrogenated Si,C,C,N-containing molecules. The knowledge of the present monohydrogenated SiC(2)N isomerism could provide useful information for more highly hydrogenated or larger Si,C(2),N-containing species.

Acetylene↗

PubMed2006

Heme oxygenase-1 enhances renal mitochondrial transport carriers and cytochrome C oxidase activity in experimental diabetes.

Up-regulation of heme oxygenase (HO-1) by either cobalt protoporphyrin (CoPP) or human gene transfer improves vascular and renal function by several mechanisms, including increases in antioxidant levels and decreases in reactive oxygen species (ROS) in vascular and renal tissue. The purpose of the present study was to determine the effect of HO-1 overexpression on mitochondrial transporters, cytochrome c oxidase, and anti-apoptotic proteins in diabetic rats (streptozotocin, (STZ)-induced type 1 diabetes). Renal mitochondrial carnitine, deoxynucleotide, and ADP/ATP carriers were significantly reduced in diabetic compared with nondiabetic rats (p < 0.05). The citrate carrier was not significantly decreased in diabetic tissue. CoPP administration produced a robust increase in carnitine, citrate, deoxynucleotide, dicarboxylate, and ADP/ATP carriers and no significant change in oxoglutarate and aspartate/glutamate carriers. The increase in mitochondrial carriers (MCs) was associated with a significant increase in cytochrome c oxidase activity. The administration of tin mesoporphyrin (SnMP), an inhibitor of HO-1 activity, prevented the restoration of MCs in diabetic rats. Human HO-1 cDNA transfer into diabetic rats increased both HO-1 protein and activity, and restored mitochondrial ADP/ATP and deoxynucleotide carriers. The increase in HO-1 by CoPP administration was associated with a significant increase in the phosphorylation of AKT and levels of BcL-XL proteins. These observations in experimental diabetes suggest that the cytoprotective mechanism of HO-1 against oxidative stress involves an increase in the levels of MCs and anti-apoptotic proteins as well as in cytochrome c oxidase activity.

Animals↗

PubMed2006

Transformation of steviol-16alpha,17-epoxide by Streptomyces griseus and Cunninghamella bainieri.

Eight new ent-beyerane metabolites, 5-8, 12, and 14-16, and four new ent-kaurane metabolites, 3, 10, 11, and 13, together with two known metabolites, 4 and 9, were isolated from the microbial transformations of steviol-16alpha,17-epoxide using Streptomyces griseus ATCC 10137 and Cunninghamella bainieri ATCC 9244. The structures of the metabolites were characterized by IR, HRFABMS, and 1D and 2D NMR data. In addition, a GRE (glucocorticoid response element)-mediated luciferase reporter assay was used to initially screen for the biological activity of the 11 metabolites and stevioside. Steviol (1), steviol-16alpha,17-epoxide (2), ent-11alpha,13,16alpha,17-tetrahydroxykauran-19-oic acid (3), ent-17-hydroxy-16-ketobeyeran-19-oic acid (4), ent-9alpha,13-dihydroxy-16beta,17-epoxykauran-19-oic acid (10), ent-9alpha,17-dihydroxy-16-ketobeyeran-19-oic acid (12), ent-1beta,17-dihydroxy-16-ketobeyeran-19-oic acid (14), and stevioside showed significant effects; in particular, stevioside showed almost equal potency as dexamethasone.

Animals↗

PubMed2005

[Study on application of Fourier transformation near-infrared spectroscopy analysis with support vector machine (SVM)].

Support Vector Machine (SVM) is a method for the research on identifying two types of problem. It is the latest branch in the statistics study theories, and the identification model has a strict mathematics foundation. In this paper, the basic principle and method of SVM are not only introduced, but also applied to chemometrics. One hundred and three rhubarb samples were used as experimental materials. The identification models were established with near-infrared spectroscopy and SVM training method with the intention of identifying whether the rhubarb samples are true or false. The thirty-three samples in training set were identified by the identifying models with the accurate rate of 100%, while seventy estimate samples had an accurate rate of 96.77%. The research result provided the method of identifying the traditional Chinese medicine rhubarb quickly. So, it shows the feasibility of establishing the models with near-infrared spectroscopy and SVM method to identify biological samples. This paper introduced the theme of SVM training method in order to beget the attention of the research members who deal with chemometrics.

Algorithms↗

PubMed2005

[An applied study on Fourier transform near-infrared whole spectroscopy regression analysis].

In the present paper, 66 wheat samples were used as experimental materials, 33 of them were used for building the quantitative analysis model of protein content, and the rest composed the prediction set. Using Moore-Penrose matrix, we estimated directly the regression coefficients of the regression analysis model with Fourier transform near-infrared (FTNIR) whole spectroscopy. The samples of prediction set were analyzed, and the correlation coefficient is 0.979 9 between the prediction values of the near-infrared model and the standard chemical ones by Kjeldahl's method, and the average relative error is 1.76%. Using Moore-Penrose matrix, we can not only get the near-infrared spectroscopy analysis model's regression coefficients, but also know their contribution at every wavelength point. Consequently we can understand and explain the physical and chemical significance of the FTNIR whole spectroscopy regression model.

Plant Proteins↗

PubMed2004

Andrographolide acts through inhibition of ERK1/2 and Akt phosphorylation to suppress chemotactic migration.

We now evaluated the anti-inflammatory mechanisms of andrographolide on complement 5a (C5a)-induced macrophage recruitment in vitro. Andrographolide concentration dependently inhibited cell migration toward C5a with an IC50 of 5.6+/-0.7 microM. With relatively specific kinase inhibitors (PD98059, SB203580, SP600125, wortmannin and LY294002, respectively) the results showed that extracellular signal-regulated kinase1/2 (ERK1/2), p38 mitogen-activated protein kinase (p38 MAPK) and phosphatidylinositol-3-kinase (PI3K) were necessary for C5a-induced migration, whereas c-Jun N-terminal kinase (JNK) was nonessential. Andrographolide significantly attenuated C5a-stimulated phosphorylation of ERK1/2, and of its upstream activator, MAP kinase-ERK kinase (MEK1/2). C5a-activated ERK1/2 phosphorylation was 86+/-9% inhibited by 30 microM andrographolide. Under the same conditions, however, andrographolide failed to affect C5a-stimulated p38 MAPK and JNK phosphorylation. Andrographolide also strongly abolished C5a-stimulated Akt phosphorylation, a downstream target protein for PI3K. These results indicate that inhibition of cell migration by interfering with ERK1/2 and PI3K/Akt signal pathways may contribute to the anti-inflammatory activity of andrographolide.

Androstadienes↗

PubMed2004

Abeta aggregation inhibitors. Part 1: Synthesis and biological activity of phenylazo benzenesulfonamides.

Phenylazo benzenesulfonamides were designed and synthesized as beta-amyloid (Abeta40) fibril assembly inhibitors, and evaluated for inhibition of Abeta40 aggregation and neurotoxicity using rat cortical neurons. Compound 2 (LB-152) was the most potent compound in this study, and the para-NMe(2) group on the end of the phenylazo moiety may play an important role in preventing Abeta40 fibril formation. LB-152 provides a new lead for further development of potential beta-amyloid aggregation inhibitors to treat AD.

Amyloid beta-Peptides↗

PubMed2004

C5a differentially stimulates the ERK1/2 and p38 MAPK phosphorylation through independent signaling pathways to induced chemotactic migration in RAW264.7 macrophages.

We elucidate the roles of various protein kinases involved in complement 5a (C5a)-induced cell migration. Results showed that extracellular signal-regulated kinase1/2 (ERK1/2), p38 mitogen-activated protein kinase (p38 MAPK) and phosphatidylinositol 3-kinase (P13K) were necessary for C5a-induced migration, whereas protein kinase C and c-Jun N-terminal kinase (JNK) were nonessential. C5a-induced migration was also suppresses by phospholipase C (PLC) inhibitor U73122 and pertussis toxin (PTX). We found that C5a-induced, time-dependent (1) ERK1/2 phosphorylation was markedly diminished by PTX, U73122, P13K inhibitors wortmannin and LY294002 and ERK1/2 inhibitor PD98059; (2) Akt phosphorylation was also attenuated by the above inhibitors except PD98059; (3) p38 MAPK phosphorylation was only affected by PTX. Furthermore, C5a also stimulated PLCbeta(2) membrane translocation in a time-dependent manner that occurred early prior to Akt phosphorylation and could be abolished only by PTX and U73122. These results suggest that C5a, through the activation of PTX-sensitive G protein, to differentially stimulate ERK1/2 and p38 MAPK phosphorylation and evoke cell migration. That is, ERK1/2 but not p38 MAPK phosphorylation is down stream of P13K/Akt and modulated by PLC. Additionally, beta(2) isoform may be one of the participates in C5a signal and acts more upstream of P13K/Akt.

Animals↗

PubMed2004

Hydroxylation and glucosidation of ent-16beta-Hydroxybeyeran-19-oic acid by Bacillus megaterium and Aspergillus niger.

ent-16beta-Hydroxybeyeran-19-oic acid ( 1) has potential antihypertensive activity. To obtain novel and more-effective compounds, 1 was incubated with Bacillus megaterium ATCC 14 581 and Aspergillus niger CCRC 32 720. The structures of the metabolites were determined by HR-FAB-MS, 1D- and 2D-NMR spectral data, and enzymatic hydrolysis. Bacillus megaterium hydroxylated and glucosidated 1 to yield ent-7alpha,16beta-dihydroxybeyeran-19-oic acid ( 2), ent-16beta-hydroxybeyeran-19-oic acid alpha- D-glucopyranosyl ester ( 3), and ent-7alpha,16beta-dihydroxybeyeran-19-oic acid alpha- D-glucopyranosyl ester ( 4). Aspergillus niger hydroxylated 1 to yield ent-1beta,7alpha,16beta-trihydroxybeyeran-19-oic acid ( 5) and ent-1beta,7alpha-dihydroxy-16-oxobeyeran-19-oic acid ( 6). Metabolites 3 - 5 were characterized as new compounds. In addition, 2, 3, 5, and 6 were tested for antihypertensive effects, and we found that 5 and 6 were more potent than the parent compound 1.

Antihypertensive Agents↗

PubMed2004

Isolation and immunomodulatory effect of flavonoids from Syzygium samarangense.

Sixteen flavonoids were isolated from the acetone extract of the leaves of Syzygium samarangense Merr. et Perry. The isolated flavonoids were evaluated for immunopharmacological activity. Human peripheral blood mononuclear cells (PBMC) were used as target cells, and cell proliferation was determined by 3H-thymidine uptake. Among them, (-)-strobopinin (2), myricetin 3-O-(2''-O-galloyl)-alpha-rhamnopyranoside (8), (-)-epigallocatechin 3- O-gallate (10) and myricetin 3-O-alpha-rhamnopyranoside (11) showed inhibitory potency on PBMC proliferation activated by phytohemagglutinin (PHA). The IC50 values of compounds 2, 8, 10, and 11 on activated PBMC proliferation were 36.3, 11.9, 28.9, and 75.6 microM, respectively. The inhibitory mechanisms may involve the blocking of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) production, since compounds 2, 8, 10 and 11 reduced IL-2 and IFN-gamma production in PBMC in a dose-dependent manner.

Cell Proliferation↗

PubMed2003

FT-IR spectroscopic analysis of normal and cancerous tissues of esophagus.

AIM: To investigate the special Fourier transform infrared spectroscopy (FT-IR) spectra in normal and cancerous tissues of esophagus. METHODS: Twenty-seven pairs of normal and cancerous tissues of esophagus were studied by using FT-IR and the special spectra characteristics were analyzed in different tissues. RESULTS: Different spectra were found in normal and cancerous tissues. The peak at 1 550/cm was weak and wide in cancerous tissues but strong and high in normal tissues. The ratio of I 1 647/I 1 550 was 2.0 in normal tissues and 2.36 in cancerous tissues (P<0.05). The ratio of I 1 550/I 1 080 was 4.5 in normal tissues and 3.4 in cancerous tissues (P<0.01). The peak at 1453 /cm was higher than at 1 402/cm in normal tissue and lower than at 1 402/cm in cancerous tissues. CONCLUSION: The results indicate that FTIR may be used in clinical diagnosis.

Case-Control Studies↗

PubMed2002

Antitumor agents. Part 3: synthesis and cytotoxicity of new trans-stilbene benzenesulfonamide derivatives.

A new series of trans-stilbene benzenesulfonamide derivatives were designed and synthesized as potential antitumor agents. These new compounds were evaluated in the National Cancer Institute's 60 human tumor cell line in vitro screen. Compounds 9-13 were cytotoxic against several cell lines. Notably, two compounds, 9 and 12, demonstrated selective cytotoxic activity against BT-549 breast cancer (GI(50)=0.205 microM) and HT-29 colon cancer (GI(50)=0.554 microM), respectively.

Antineoplastic Agents↗

PubMed2002

Microbial transformations of isosteviol.

Microbial transformations of the tetracyclic diterpenoid isosteviol (ent-16-ketobeyeran-19-oic acid) (2) have revealed that isosteviol is metabolized by Cunninghamella bainieri, Actinoplanes sp., Mucor recurvatus, and Cunninghamella blakesleeana to yield five new metabolites, ent-11alpha,12alpha-dihydroxy-16-ketobeyeran-19-oic acid (5), ent-11alpha,12alpha,17-trihydroxy-16-ketobeyeran-19-oic acid (6), ent-12alpha,15alpha-dihydroxy-16-ketobeyeran-19-oic acid (7), ent-7alpha,15alpha-dihydroxy-16- ketobeyeran-19-oic acid (8), and ent-9alpha-hydroxy-16-ketobeyeran-19-oic acid (9), together with three known metabolites, ent-7alpha-hydroxy-16-ketobeyeran-19-oic acid (3), ent-7beta-hydroxy-16-ketobeyeran-19-oic acid (4), and ent-12alpha-hydroxy-16-ketobeyeran-19-oic acid (10). The structures of these metabolites were established on the basis of HRFABMS and 1D and 2D NMR spectral data. In addition, metabolites 3-10 were tested for antihypertensive activity and were found to be less active than the parent compound 2.

Antihypertensive Agents↗