Discovery of potential Toxoplasma gondii CDPK1 inhibitors with new scaffolds based on the combination of QSAR and scaffold-hopping method with in vitro validation.

To discover drugs for toxoplasmosis with less side-effects and less probability to get drug resistance is eagerly appealed for pregnant women, infant or immunocompromised patients. In this work, using TgCDPK1 as drug target, we design a method to discover new inhibitors for CDPK1 as potential drug lead for toxoplasmosis with novel scaffolds based on the combination of 2D/3D-QSAR and scaffold-hopping methods. All the binding sites of the potential inhibitors were checked by docking method, and only the ones that docked to the most conserved sites of TgCDPK1, which make them have less probability to get drug resistance, were remained. As a result, 10 potential inhibitors within two new scaffolds were discovered for TgCDPK1 with experimentally verified inhibitory activities in micromole level. The discovery of these inhibitors may contribute to the drug development for toxoplasmosis. Besides, the pipeline which is composed in this work as the combination of QSAR and scaffold-hopping is simple, easy to repeat for researchers without need of in-depth knowledge of pharmacology to get inhibitors with novel scaffolds, which will accelerate the procedure of drug discovery and contribute to the drug repurposing study.

Characterization of the genome of a Nocardia strain isolated from soils in the Qinghai-Tibetan Plateau that specifically degrades crude oil and of this biodegradation.

A strain of Nocardia isolated from crude oil-contaminated soils in the Qinghai-Tibetan Plateau degrades nearly all components of crude oil. This strain was identified as Nocardia soli Y48, and its growth conditions were determined. Complete genome sequencing showed that N. soli Y48 has a 7.3 Mb genome and many genes responsible for hydrocarbon degradation, biosurfactant synthesis, emulsification and other hydrocarbon degradation-related metabolisms. Analysis of the clusters of orthologous groups (COGs) and genomic islands (GIs) revealed that Y48 has undergone significant gene transfer events to adapt to changing environmental conditions (crude oil contamination). The structural features of the genome might provide a competitive edge for the survival of N. soli Y48 in oil-polluted environments and reflect the adaptation of coexisting bacteria to distinct nutritional niches.

Complete genome sequence of a psychotrophic Pseudarthrobacter sulfonivorans strain Ar51 (CGMCC 4.7316), a novel crude oil and multi benzene compounds degradation strain.

Pseudarthrobacter sulfonivorans strain Ar51, a psychotrophic bacterium isolated from the Tibet permafrost of China, can degrade crude oil and multi benzene compounds efficiently in low temperature. Here we report the complete genome sequence of this bacterium. The complete genome sequence of Pseudarthrobacter sulfonivorans strain Ar51, consisting of a cycle chromosome with a size of 5.04Mbp and a cycle plasmid with a size of 12.39kbp. The availability of this genome sequence allows us to investigate the genetic basis of crude oil degradation and adaptation to growth in a nutrient-poor permafrost environment.

Complete genome sequence of Acinetobacter sp. TTH0-4, a cold-active crude oil degrading strain isolated from Qinghai-Tibet Plateau.

Acinetobacter sp. strain TTH0-4 was isolated from a permafrost region in Qinghai-Tibet Plateau. With its capability to degrade crude oil at low temperature, 10°C, the strain could be an excellent candidate for the bioremediation of crude oil pollution in cold areas or at cold seasons. We sequenced and annotated the whole genome to serve as a basis for further elucidation of the genetic background of this promising strain, and provide opportunities for investigating the metabolic and regulatory mechanisms and optimizing the biodegradative activity in cold environment.

[Effect of edaravone on oxidative stress and myocardial fibrosis induced by isoproterenol in rats].

OBJECTIVE: To investigate the effect of edaravone on oxidative stress and myocardial fibrosis induced by isoproterenol in rats. METHODS: Fifty male SD rats were randomly divided into 5 groups, including a control group, a myocardial fibrosis model (established by injections of isopropyl adrenaline for 10 days) group, and 3 edaravone groups with edaravone treatment at low, medium, or high doses for 14 days. After the treatments, the rats were examined for the degree of myocardial fibrosis, left ventricular mass index (LVMI), collagen volume fraction (CVF), and myocardial contents of collagen I (Col I), collage III (Col III), hydroxyproline (Hyp), superoxide dismutase (SOD), malondialdehyde (MDA), and nitric oxide (NO); The expression of transforming growth factor-ß1 (TGF-ß1) in the myocardial tissues was examined by immunofluorescence assay and Western blotting. RESULTS: Compared with the control rats, the rat models of myocardial fibrosis showed significantly increased CVF and LVMI (P=0.000), which were lowered by edaravone treatments in a dose-dependent manner (P<0.05). The myocardial contents of Col I, Col III and Hyp also increased in the model group (P=0.000) and were lowered dose-dependently by edaravone; the contents of MDA was higher (P=0.000) and SOD and NO were lower in the model group (P=0.000), and edaravone treatments obviously increased SOD and NO contents (P<0.05). The model rats showed significantly increased myocardial expression of TGF-ß1 (P=0.000), which was markedly lowered by edaravone treatments (P=0.000). The myocardial content of MDA was positively correlated while SOD and NO were negatively with LVMI, CVF, Col I, Col III and Hyp; TGF-ß1 was positively correlated with LVMI, CVF, Col I, Col III, Hyp and MDA but negatively with SOD and NO. CONCLUSION: Edaravone can relieve oxidative stress and inhibit TGF-ß1 activation to ameliorate myocardial fibrosis in rats.

[Changes of IFN-gamma, IL-2, IL-6 and IL-10 in the patient with cardiac surgery under combined acupuncture anesthesia].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on cytokines in the cardiac surgical patient and to evaluate the application of combined acupuncture anesthesia to cardiac surgery. METHODS: Thirty patients with atrial septal defect were divided into 3 groups, general anesthesia group (A), acupuncture anesthesia group (B) and combined general anesthesia and EA group (C). Peripheral blood samples were collected before anesthesia, before cardiopulmonary bypass (CPB), 30 min after CPB and 24 h after operation to determine the levels of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-6 and IL-10. RESULTS: The levels of IFN-gamma and IL-2 decreased in the 3 groups after CPB and further decreased 24 h after operation, and in the group C were higher than those in the group B. The levels of IL-6 and IL-10 significantly increased 24 h after operation in the 3 groups with no significant difference among the 3 groups. CONCLUSION: The general anesthesia combined with EA can not completely improve the decrease of IFN-gamma and IL-2 induced by CPB, indicating that the good response of the general anesthesia combined with EA to stress can partially improve the immunosupression induced by CPB. Acupuncture does not have significant effect on inflammatory cytokine reaction induced by cardiac surgery.