Vascular endothelial cell injury or dysfunction has been implicated in the onset and' progression of cardiovascular diseases including atherosclerosis. A number of previous studies have demonstrated that the pro-oxidative and pro-inflammatory pathways within vascular endothelium play an important role in the initiation and progression of atherosclerosis, Recent evidence has provided compelling evidence to indicate that interleukin-4 (IL-4) can induce proc inflammatory environment via oxidative stress-mediated up-regulation of inflammatory mediators such as cytokine, chemokine, and adhesion molecules in vascular endothelial cells. In addition, apoptotic cell death within vascular endothelium has been hypothesized to be involved in the development of atherosclerosis. Emerging evidence has demonstrated that IL-4 can induce apoptosis of human vascular endothelial cells through the caspase-3-dependent pathway, suggesting that IL-4 can increase endothelial cell turnover by accelerated apoptosis, the event which may cause the dysfunction of the vascular endothelium. These studies will have a high probability of revealing new directions that lead to the development of clinical strategies toward the prevention and/or treatment for individuals with inflammatory vascular diseases including atherosclerosis.

A novel series of 1-(1-benzofuran-2-yl-ethylidene)-4-substituted thiosemicarbazides (2a-d) along with some derived ring systems: substituted-2,3-dihydro-thiazoles(3a-c, 4a-f) and thiazolidin-4-ones(5a-d and 6a-d), were synthesized. In addition, cyanoacetic acid-(1-benzofuran-2-yl-ethylidene) hydrazide(7) was used to prepare another new series of compounds consisting of substituted pyridin-2(1H)-ones(8a-c); 2-thioxo-2,3-dihydro-thiazoles(9a-d) and 2-thioxo-2,3-dihydro-6H-thiazolo[4,5-d]pyrimidin-7-ones (10a-c, 11a-c). The absolute configuration of compound 5c was determined by X-ray crystallography. The compounds prepared were evaluated for their in vitro anti-HIV, anticancer, antibacterial, and antifungal activities. Among the tested compounds, compounds 5c and 9a produced a significant reduction ㅐ ㄹ the viral cytopathic effect (93.19% and 59.55%) at concentrations $>2.0{\times}10^{-4}\;M\;and\;2.5{\times}10^{-5}\;M$respectively. Compound 9a was confirmed to have moderate anti-HIV activity. Compounds 2a, 2d, and 5c showed mild antifungal activity. However, none of the tested compounds showed any significant anticancer activity.

Some new derivatives of 1,2,4-triazolo[2,3-a]benzimidazoles were synthesized through the reaction of 1,2-diaminobenzimidazole with carbon disulfide. The resulting 1,2,4-triazolo-[2,3a]benzimidazole-2-thione intermediate was reacted with one equivalent of alkyl halides to give the corresponding 2-alkylthio derivatives, which were further alkylated through the reaction with another one equivalent of different alkyl halides to afford the target compounds; 1-alkyl-2alkylthio-1,2,4-traizolo[2,3-a]benzimidazoles. On the other hand, the 1,2-disubstituted derivatives with two identical alkyl substituents were prepared by the reaction of 1,2,4-triazolo[2,3-a]benzimidazole-2-thione with two equivalents of the alkyl halides. The structures of the new compounds were assigned by spectral and elemental methods of analyses. The synthesized compounds were tested for their antibacterial and antifungal activities. Most of the tested compounds proved comparable results with those of ampicillin and fluconazole reference drugs. The study indicated that, the antibacterial as well as the antifungal activities of the test compounds were improved with increase in the bulkiness of the introduced alkyl groups. Also, some active antibacterial compounds were tested for their antimycobacterial activity. All the test compounds showed equipotent antitubercular activity as that of INH as a reference drug.

The antispasmodic and vasodilator activities of a newly synthesized piperidine derivative (1-(4'fluorophenacyl)-4-hydroxy-4-phenyl-piperidinium chloride) were studied in vitro. The test compound exhibited a dose-dependent relaxant effect on the spontaneous and $K^+$ (75 mM)-induced contractions of isolated rabbit jejunum with respective $EC_{50}$ values of 0.01 mM(0.01-0.02, 95% CI) and 0.30 mM (0.17-0.56). The $Ca^{++}$ channel blocking (CCB) activity was confirmed when the test compound (0.1-0.2 mM) shifted the $Ca^{++}$ dose-response curves to the right, similar to that produced by verapamil ($0.1-1.0{\mu}M$), a standard CCB. In the isolated rabbit aorta, the test compound showed a dose-dependent vasodilator effect on $K^+$ (75 mM)-induced contractions with an $EC_{50}$ value of 0.08 mM (0.02-0.26) while also suppressed the norepinephrine ($1{\mu}M$) control peak responses with $EC_{50}$ value of 0.08 mM (0.05-0.13, n=5). When tested in Langendorff perfused rabbit heart preparation, the test compound exhibited a negligible inhibitory effect on the rate or force of atrial and ventricular contractions when tested up to 5 mM. The results show smooth muscle-selective relaxant effect of the test compound on intestinal and vascular preparations mediated possibly via blockade of voltage and receptor-operated $Ca^{++}$ channels.

Several diacetoxy acetal analogues have been synthesized from santonin and assessed for their ability of inducing or enhancing the differentiation of human HL-60 leukemia cells. The compounds themselves had little effect on HL-60 cell differentiation. However, three analogues, 2a, 3a, and 5b, synergistically enhanced 1,25-dihydroxyvitamin $D_3[1,25-(OH)_2D_3]-induced$ HL-60 cell differentiation when combined with 5 nM of dihydroxyvitamin $D_3[1,25(OH)_2O_3]$, a well-known differentiation inducer. Especially, the compound 5b profoundly enhanced the $1,25-(OH)2O_3]-induced$ HL-60 cell differentiation.

In this study, 2-N-arylimino-2,3-dihydro-1,3,4-thiadiazoles derivatives (6a-h) were synthetized. The mechanism of the studied reactions was discussed. The chemical structures of the compounds were elucidated by their IR, $^1H-NMR,\;^{13}C-NMR$, and Mass spectral data and elemental analyses. The compounds were tested for antimicrobial activity using diffusion agar technique.

Translationally controlled tumor protein (TCTP), also known as histamine releasing factor (HRF), is found abundantly in different eukaryotic cell types. The sequence homology of TCTP between different species is very high, belonging to the MSS4/DSS4 superfamily of proteins. TCTP is involved in both cell growth and human late allergy reaction, as well as having a calcium binding property; however, its primary biological functions remain to be clearly elucidated. In regard to many possible functions, the TCTP of Plasmodium falciparum (Pf) is known to bind with an antimalarial agent, artemisinin, which is activated by heme. It is assumed that the endoperoxide-bridge of artemisinin is opened up by heme to form a free radical, which then eventually alkylates, probably to the Cys14 of PfTCTP. Study of the docking of artemisinin with heme, and subsequently with PfTCTP, was carried out to verify the above hypothesis on the basis of structural interactions. The three dimensional (3D) structure of PfTCTP was built by homology modeling, using the NMR structure of the TCTP of Schizosaccharomyces pombe as a template. The quality of the model was examined based on its secondary structure and biological function, as well as with the use of structure evaluating programs. The interactions between artemisinin, heme and PfTCTP were then studied using the docking program, FlexiDock. The center of the peroxide bond of artemisinin and the Fe of heme were docked within a short distance of $2.6{\AA}$, implying the strong possibility of an interaction between the two molecules, as proposed. When the activated form of artemisinin was docked on the PfTCTP, the C4-radical of the drug faced towards the sulfur of Cys14 within a distance of $2.48{\AA}$, again suggesting the possibility of alkylation having occurred. These results confirm the proposed mechanism of the antimalarial effect of artemisinin, which will provide a reliable method for establishing the mechanism of its biological activity using a molecular modeling study.

Secalonic acid D(SAD) was isolated as the major secondary metabolite of the marine lichen-derived fungus Gliocladium sp. T31. Its structure was established on the basic of physicochemical and spectroscopic data. This is the first report on the isolation of SAD from this fungus, as well as its inhibitory effect on K562 cell cycle and its cytotoxicity against several tumor cell lines in vitro.

The methanolic extract of the aerial parts of Centipeda minima was found to show inhibitory activity on farnesyl protein transferase (FPTase). Bioassay-guided fractionation of the methanolic extract resulted in the isolation of 6-O-angeloylprenolin, as an inhibitor on FPTase. This compound inhibited FPTase activity in a dose-dependent manner, and the $IC_{50}$ value of 6-O-angeloylprenolin was 18.8 ${\mu}M$.

The abnormal proliferation of aortic vascular smooth muscle cells (VSMCs) plays a central role in the pathogenesis of atherosclerosis and restenosis after angioplasty and possibly also in the development of hypertension. The present study was designed to examine the inhibitory effects and the mechanism of luteolin 7-glucoside (L7G) on the platelet-derived growth factor (PDGF)-BB-induced proliferation of VSMCs. L7G significantly inhibited the PDGF-BB-induced proliferation and the DNA synthesis of the VSMCs in a concentration-dependent manner. Pre-incubation of the VSMCs with L7G significantly inhibited the PDGF-BB-induced extracellular signal-regulated kinase 1/2 (ERK1/2), Akt and the phospholipase C $(PLC)-{\gamma}1$ activation. However, L7G had almost no affect on the phosphorylation of $PDGF-{\beta}$ receptor tyrosine kinase, which was induced by PDGF-BB. These results suggest that L7G inhibits the PDGF-BB-induced proliferation of VSMCs via the blocking of $(PLC)-{\gamma}1$, Akt, and ERK1/2 phosphorylation.

This investigation was undertaken to study the effects of oral administration (3 weeks) of Collybia confluens mycelial powder (CCMP) produced by a submerged culture on plasma glucose and other biochemical parameters in streptozotocin (STZ)-induced diabetic rats. Antidiabetic and hypolipidemic effects were proportionally increased with the increasing concentration of the CCMP for oral administration. The CCMP, at the dose of 400 mg/kg BW, substantially reduced the plasma glucose level by as much as 33.1 % as compared to the STZ-induced diabetic rats group. It also lowered the plasma total cholesterol, triglyceride, and low density lipoprotein (LDL) cholesterol by 22.9%, 19.9%, and 37.3%, respectively. The levels of total cholesterol and triglyceride in liver were reduced to the extent of by 13.5% and 18.8%, and the activity of alanine transaminase (ALT) and aspartate transaminase (AST) was decreased by 48.8% and 37.2%, respectively, under the influence of CCMP. The general components of CCMP were found to contain 26.18% carbohydrate, 3.67% crude ash, 4.02% crude fat, 22.55% crude protein, and 43.58% dietary fiber. The amino acid composition of the CCMP was also analyzed in detail.

Leukemias are common worldwide. Wilms'tumor1 (WT1) protein is highly expressed in leukemic blast cells of myeloid and lymphoid origin. Thus, WT1 mRNA serves as a tumor marker for leukemias detection and monitoring disease progression. Curcumin is well known for its anticancer property. The objective of this study was to investigate the effect of curcumin on WT1 gene expression in patient leukemic cells. The leukemic cells were collected from 70 childhood leukemia patients admitted at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand, in the period July 2003 to February 2005. There were 58 cases of acute lymphoblastic leukemia (ALL), 10 cases of acute myeloblastic leukemia (AML), and 2 cases of chronic myelocytic leukemia (CML). There were 41 males and 29 females ranging from 1 to 15 years old. Leukemic cells were cultured in the presence or absence of 10 mM curcumin for 48 h. WT1 mRNA levels were determined by RT-PCR. The result showed that curcumin reduced WT1 gene expression in the cells from 35 patients (50%). It affected the WT1 gene expression in 4 of 8 relapsed cases (50%), 12 of 24 cases of drug maintenance (50%), 7 of 16 cases of completed treatment (44%), and 12 of 22 cases of new patients (54%). The basal expression levels of WT1 gene in leukemic patient cells as compared to that of K562 cells were classified as low level (1-20%) in 6 of 20 cases (30%), medium level (21-60%) in 12 of 21 cases (57%), and high level (61-100%) in 17 of 23 cases (74%). In summary, curcumin decreased WT1 mRNA in patient leukemic cells. Thus, curcumin treatment may provide a lead for clinical treatment in leukemic patients in the future.

Analysis of molecular nature of mitochondrial DNA (mtDNA) could be powerful marker for anthropological studies of modern populations. While population genetic studies on mtDNA have been reported for several ethnic groups, no such study has been documented for the Korean population. We surveyed mtDNA polymorphisms in the HVS I of noncoding D-loop region and its upstream region from 430 unrelated healthy Korean population by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing analysis. PCR product with 2,790 bp spanning the specific mtDNA region (mt13715-16504) was subjected to RFLP analysis using 6 restriction enzyme (Hinf I, Hae III, Alu I, Dde I, Mbo I, Rsa I). On the PAUP analysis of PCR-RFLP results, 38 mtDNA haplotypes (Hap 1-38) were detected in the Korean populations, which were classified into 11 haplogroups (Grp 1-11) of related haplotypes encompassing all 38 haplotypes. In comparison of sequencing data with Anderson's reference sequence, the transition type was more prevalent than the transversion type. Insertions or deletions were not found. In addition, three of the polymorphic sites (A16240C, A16351G, G16384A) in HVS-I region are determined newly. The polymorphic sites were distributed randomly in the region, though the frequency at each site was variable. Thus, this research might be required for the genealogical study of Orientals.

Phytoestrogens have been used as a food supplement to prevent osteoporosis. The isoflavones in the phytoestrogens are daidzein, genistein and formononetin which are present in various herbs. This study examined the quantity of isoflavones in medicinal herbs, which can be used as a phytoestrogen supplement; soybean. These isoflavones were quantified using high performance liquid chromatography (HPLC) with a UV/VIS detector. The concentration of daidzein in Puerariae Radix was $10,436.16{\pm}2,143.83\;mg/kg$ of the dried herb, which was much higher than that extracted from soybeans, $341.47{\pm}18.96\;mg/kg$. The amount of genistein in Sophorae flavescentis Radix ($336.09{\pm}50.89mg/kg$) was approximately 11 times higher than that extracted from soybean ($30.03{\pm}7.17mg/kg$). The level of formononetin in Dalbergiae odoriferae Lignum, $2,189.14{\pm}136.46mg/kg$, was the highest among the herbs tested. The total isoflavone content of Puerariae Radix was approximately 30 times higher than that extracted from soybean. Therefore, plants from the family Leguminosae, particularly Puerariae Radix, can be a good source of phytoestrogens.

The aim of present study is to investigate the effect of naringin on the pharmacokinetics of verapamil and its major metabolite, norverapamil in rabbits. The pharmacokinetic parameters of verapamil and norverapamil were determined after administering verapamil (9 mg/kg) orally to rabbits in the pretreated with naringin (1.5, 7.5, and 15 mg/kg). Naringin pretreatment significantly altered the pharmacokinetic parameters of verapamil. Compared with the control group (given verapamil alone), the $K_a,\;C_{max}$ and AUC of verapamil were significantly (p<0.05 or p<0.01) increased in the pretreatment of naringin, However there were no significant change in $T_{max}\;and\;t_{1/2}$ of verapamil. Consequently, pretreatment of naringin significantly (p<0.05, p<0.01) increased the AB% of verapamil significantly in a dose dependent manner (p<0.05 or p<0.01 ), and elevated the RB% of verapamil by 1.26- to 1.69-fold. the MR of verapamil were significantly (p<0.05) increased in the pretreatment of naringin, implying that pretreatment of naringin may effectively inhibit the CYP3A4-mediated metabolism of verapamil. In conclusion, pretreatment of naringin enhanced the oral bioavailability of verapamil. Based on these results, the verapamil dosage should be adjusted when given with naringin or a naringin-containing dietary supplement.

The economic and effective method for preparation of R-(-)-ibuprofen by diastereomer crystallization was developed. R-(-)-ibuprofen was resolved from racemic ibuprofen by forming R-(-)ibuprofen-R-(+)-$\alpha$-methylbenzylamine diastereomeric salt with R-(+)-$\alpha$-methylbenzylamine and crystallization. The purity of R-(-)-ibuprofen-R-(+)-$\alpha$-methylbenzylamine diastereomeric salt was tested and confirmed using HPLC and $^1H-NMR$ method. The pure diastereomeric salt collected from repeated recrystallization was further fractionated by liquid-liquid extraction to the pure enantiomer without racemization. R-(-)-ibuprofen was recovered producing overall yield of 2.4% with the purity more than 99.97%.