Computational determination of hERG-related cardiotoxicity of drug candidates.

Background: Drug candidates often cause an unwanted blockage of the potassium ion channel of the human ether-a-go-go-related gene (hERG). The blockage leads to long QT syndrome (LQTS), which is a severe life-threatening cardiac side effect. Therefore, a virtual screening method to predict drug-induced hERG-related cardiotoxicity could facilitate drug discovery by filtering out toxic drug candidates.

In silico prediction of potential chemical reactions mediated by human enzymes.

Background: Administered drugs are often converted into an ineffective or activated form by enzymes in our body. Conventional in silico prediction approaches focused on therapeutically important enzymes such as CYP450. However, there are more than thousands of different cellular enzymes that potentially convert administered drug into other forms.

ANTI-NOCICEPTIVE EFFECT OF AGRIMONIA EUPATORIA EXTRACT ON A CISPLATIN-INDUCED NEUROPATHIC MODEL.

Background: Natural products including are considered an incomparable source of molecular diversity that has led to the medicines, especially for pain treatment. To investigate the antinociception of , we examined its activity in a rat model of cisplatin neuropathy.

Materials And Methods: Male Sprague-Dawley rats received intraperitoneal (i.

Antimalarial activity of nepodin isolated from Rumex crispus.

The purpose of this study is to define the antimalarial activity of Rumex crispus. To identify an active compound that is isolated from R. crispus, bioassay-based chromatographic fractionation and purification is carried out from 70 % ethanol extract of R.

Mucilaginibacter herbaticus sp. nov., isolated from the rhizosphere of the medicinal plant Angelica sinensis.

A strictly aerobic, Gram-staining-negative, non-motile and rod-shaped bacterial strain, DR-9(T), was isolated from rhizosphere soil of the medicinal herb Angelica sinensis. Strain DR-9(T) grew at 20-40 °C, at pH 4.0-9.

Protective effects of fucoidan against γ-radiation-induced damage of blood cells.

Fucoidan, a sulfated polysaccharide purified from brown algae including Fucus vesiculosus and Laminaria japonica, has a variety of biological activities, including antioxidant and antitumor activities. Here, we investigated the radioprotective effects of fucoidan on human monoblastic leukemia cell line U937. Further, animal tests were carried out using Balb/c mice in order to determine the radiation-induced changes in the counts of blood cells, including thrombocytes, erythrocytes, leukocytes and hematocrit.

Identification of Streptomyces sp. KH29, which produces an antibiotic substance processing an inhibitory activity against multidrug-resistant Acinetobacter baumannii.

The Actinomycete strain KH29 is antagonistic to the multidrug-resistant Acinetobacter baumannii. Based on the diaminopimelic acid (DAP) type, and the morphological and physiological characteristics observed through the use of scanning electron microscopy (SEM), KH29 was confirmed as belonging to the genus Streptomyces. By way of its noted 16S rDNA nucleotide sequences, KH29 was found to have a relationship with Streptomyces cinnamonensis.

Radioprotective effect of cyclo(L-phenylalanyl-L-prolyl) on irradiated rat lung.

In the present study, we investigated the radioprotective effect of cyclo(L-phenylalanyl-L-prolyl) on irradiated rat lungs to determine its potential as a radioprotective agent. We found that early lung damage induced by irradiation was reduced by treatment with 40 mg/kg of cyclo(Lphenylalanyl- L-prolyl) in the latent and early pneumonitis phases. Expression of TNF-alpha and TGF-beta1 at 2 and TGF-beta1 at 8 weeks post-irradiation was decreased in animals that received both radiation and cyclo(L-phenylalanyl-L-prolyl) compared with animals that received radiation alone.

Correlative effect between in vivo hollow fiber assay and xenografts assay in drug screening.

Purpose: This study was carried out to assess the usage of an in vivo hollow fiber assay to screen drugs with highly predictive accuracy.

Materials And Methods: The assay systems used were the hollow fiber and xenografts assays. The hollow fiber assay was carried out with the following steps; preparation of fibers, preparation of cells, loading and implanting fibers, treatment with drugs, removal of fibers and assaying for the cell viability by the MTT assay.

Cyclic dipeptides exhibit synergistic, broad spectrum antimicrobial effects and have anti-mutagenic properties.

Cyclic dipeptides are known to have antiviral, antibiotic and antitumour properties. The aim of this study was to determine the combined effects of cyclo(L-leucyl-L-prolyl) and cyclo(L-phenylalanyl-L-prolyl) on the growth of vancomycin-resistant enterococci (VRE) and pathogenic yeasts, as well as determining their anti-mutagenic effects. This drug combination was especially effective against five VRE strains: Enterococcus faecium (K-99-38), E.

Cloning, expression, and characterization of 5-aminolevulinic acid synthase from Rhodopseudomonas palustris KUGB306.

The hemA gene encoding 5-aminolevulinic acid synthase (ALAS) was cloned from the genomic DNA of photosynthetic bacterium Rhodopseudomonas palustris KUGB306. The deduced protein (ALAS) of this gene contained 409 amino acids. The hemA gene was subcloned into an expression vector pGEX-KG and the encoded protein was overexpressed as a fusion protein with glutathione-S-transferase (GST) in Escherichia coli BL21.

Differential distribution of GABA(B1) and GABA(B2) receptor mRNAs in the rat brain.

Gamma-aminobutyric acid receptors (GABA(B)Rs) are G-protein coupled receptors mediating the slow-onset and prolonged synaptic actions of GABA in the central nervous system (CNS). There are two subtypes, GABA(B1)R and GABA(B2)R, that are though to form heterodimers, with the GABA(B1)R subunit essential for ligand binding and the GABA(B2)R subunit for cell surface localization. We have analyzed the distribution of GABA(B1)R and GABA(B2)R transcripts by in situ hybridization.

Inhibition of complement activation by recombinant Sh-CRIT-ed1 analogues.

Sh-CRIT-ed1 is a potent anti-complement peptide that inhibits the classical complement-activation pathway by interfering with the formation of the C3-convertase complex, C4b2a. C2 is an essential serum glycoprotein that provides the catalytic subunit of the C3 and C5 convertases of the classical pathways of complement activation. Because only in its C4-bound state is C2a capable of cleaving its physiological protein substrates C3 and C5, the interaction of Sh-CRIT-ed1 with C2 plays a decisive role of inhibition in the classical complement-activation process.

Isolation and characterization of Streptomyces sp KH-614 producing anti-VRE (vancomycin-resistant enterococci) antibiotics.

The actinomycete strain KH-614 was antagonistic to vancomycin-resistant enterococci (VRE). Based on the diaminopimelic acid (DAP) type, morphological and physiological characteristics examined by scanning electron microscopy (SEM), KH-614 was confirmed as belonging to the genus Streptomyces. Based on the 16S rDNA nucleotide sequences, Streptomyces sp.

Caffeine-induced neuronal death in neonatal rat brain and cortical cell cultures.

We examined the potential neurotoxicity of caffeine and. Intraperitoneal administration of caffeine (50 mg/kg, 3 times a day) produced neuronal death in various brain areas of neonatal rats 24 h later. Caffeine at doses > 300 microM was also neurotoxic in murine cortical cell cultures.

A hot pepper cDNA encoding ascorbate peroxidase is induced during the incompatible interaction with virus and bacteria.

Capsicum annuum L. is infected by a number of viruses, including the tobacco mosaic virus (TMV). To study the defense-related genes that are induced by TMV in hot peppers, the pepper plant, which is susceptible to P1.

Refolding of the catalytic and hinge domains of human MT1-mMP expressed in Escherichia coli and its characterization.

The catalytic and hinge domain (Tyr112-Ile318) of the human membrane type-1 matrix metalloproteinase (MT1-MMP; MMP-14), containing hexa-histidines at the C-terminus (chMT1-MMP), was overexpressed in Escherichia coli. The expressed polypeptide was almost exclusively found in the inclusion body, and then purified by a single Ni2+-NTA agarose column chromatography after solubilization with 6 M urea. During refolding, the 26.