Jochumsenworm1181

litis.

Coronary artery disease (CAD) and stroke are major causes of cardiovascular diseases related deaths. Conventional risk factors cannot explain the changes in atherosclerosis. New and useful diagnostic markers are required. MicroRNAs are small, noncoding RNA that regulate the gene expression implicated in the pathogenesis of various cardiovascular diseases. Endothelial dysfunction is involved in the early event of the atherosclerosis process.

The current study was designed to evaluate the vascular endothelium-enriched miRNAs would be altered in CAD patients.

Circulating miR-126 & 122 levels were measured in serum from 78 CAD patients and 60 non CDA patients by qRT-PCR analysis.

MiR-122 was significantly down regulated in CAD patients (p = 0.001), however the level of miR-126 did not show any change (p = 0.507). Remarkably, the level of miR-126 was significantly decreased in patients with CAD and high small dense low density lipoprotein (sdLDL) level. The level of miR-126 was significantly increased role in cholesterol biosynthesis and deteriorates the cardiovascular system through the process of inflammation, apoptosis, oxidative stress and ECM deposition in a number of cardiovascular diseases.A series of 11 3-(ω-aminoalkoxy)-1-benzyl-5-nitroindazoles (2-12) has been prepared starting from 1-benzyl-5-nitroindazol-3-ol 13, and evaluated against sensitive and resistant isolates of the sexually transmitted protozoan Trichomonas vaginalis. Compounds 2, 3, 6, 9, 10 and 11 showed trichomonacidal profiles with IC50 less then 20 µM against the metronidazole-sensitive isolate. Moreover, all these compounds submitted to cytotoxicity assays against mammalian cells exhibited low non-specific cytotoxic effects, except compounds 3 and 9 which displayed moderate cytotoxicity (CC50 = 74.7 and 59.1 µM, respectively). Those compounds with trichomonacidal effect were also evaluated against a metronidazole-resistant culture. Special mention deserve compounds 6 and 10, which displayed better IC50 values (1.3 and 0.5 µM respectively) than that of the reference drug (IC50 MTZ = 3.0 µM). The high activity of these compounds against the resistant isolate reinforces the absence of cross-resistance with the reference drug. The remarkable trichomonacidal results against resistant T. BMS202 in vivo vaginalis isolates suggest the interest of 3-(ω-aminoalkoxy)-1-benzyl-5-nitroindazoles to be considered as good prototypes to continue in the development of new drugs with enhanced trichomonacidal activity, aiming to increase the non-existent drugs to face clinical resistance efficiently for those patients in whom therapy with 5-nitroimidazoles is contraindicated.A series of novel indolyl-α-keto-1,3,4-oxadiazole derivatives have been synthesized by employing molecular iodine-mediated oxidative cyclization of acylhydrazones. In vitro anti cell proliferation activity of these derivatives against various cancer cells lines such as human lymphoblast (U937), leukemia (Jurkat & SB) and human breast (BT474) was investigated. Among the synthesized indolyl-α-keto-1,3,4-oxadiazoles 19a-p, only one compound (19e) exhibited significant antiproliferative activity against a panel of cell lines. The compound 19e with 3,4,5-trimethoxyphenyl motif, endowed strong cytotoxicity against U937, Jurkat, BT474 and SB cancer cells with IC50 values of 7.1, 3.1, 4.1, and 0.8 µM, respectively. Molecular docking studies suggested a potential binding mode for 19e in the colchicine binding site of tubulin. When tested for in vitro tubulin polymerizaton, 19e inhibited tubulin polymezations (IC50 = 10.66 µM) and induced apoptosis through caspase 3/7 activation. Further, the derivative 19e did not cause necrosis when measured using lactate dehydrogenase assay.Fluorescent biosensors are indispensable tools for molecular imaging, detection, and drug screening. Conventionally, fluorescent biosensors were constructed by incorporating fluorophores into ligands. Here, to develop ligand-independent biosensors, we demonstrated biosensor selection from a fluorophore-modified peptide phage library. In this library, the peptides were designed to form α-helical structures, and one cysteine, the probe modification site, was located at the center of four randomized residues on the same face of the helix. By conjugation with 4-nitrobenzoxadiazole (NBD), we constructed an NBD-modified phage library. We conducted selection against galectin-3 (Gal-3), a galactose-specific lectin associated with various biological events such as tumor metastasis and insulin resistance. After biopanning, we obtained NBD-modified peptides that selectively bind to Gal-3 from the library. The fluorescence intensity of the hit biosensors increased with the concentration of Gal-3, and this fluorescent response was visually observed.Brevinin-1BYa is an amphibian skin-derived peptide that exhibits promising anti-microbial activity against gram-positive and -negative bacteria. However, the anti-tumor activity of Brevinin-1BYa remains unclear, and, more importantly, its therapeutic application is limited owing to its poor protease and reduction stability. In this study, a series of novel Brevinin-1BYa derivatives, including O-linked N-acetyl-glucosamine glyclopeptides and disulfide bond mimetics, were designed and synthesized. Additionally, their anti-tumor activity against human prostate cancer cell line C4-2B, human NSCLC cell line A549 (adenocarcinoma), and human hepatoma cells line HuH-7 was investigated. Among these, the thioether bridge substituted peptidomimetic Brevinin-1BYa-3 displayed improved reduction stability, more stable secondary structure, greater protease stability, and increased anti-tumor activity compared with the original peptide, rendering it a promising leading compound for drug development, particularly for applications against malignant tumors.A high throughput screen (HTS) identified a novel, but weak (EC50 = 6.2 μM, 97% Glu Max) mGlu4 PAM chemotype based on a 1,4-thiazepane core, VU0544412. Reaction development and chemical optimization delivered a potent mGlu4 PAM VU6022296 (EC50 = 32.8 nM, 108% Glu Max) with good CNS penetration (Kp = 0.45, Kp,uu = 0.70) and enantiopreference. Finally, VU6022296 displayed robust, dose-dependent efficacy in reversing Haloperidol-Induced Catalepsy (HIC), a rodent preclinical Parkinson's disease model.