Selectivity mechanism of BCL-XL/2 inhibition through investigation.

The BCL-XL protein is among the most important members of the anti-apoptotic subfamily of the BCL-2 protein family, and is currently a promising new target for anti-tumor drug research. However, the BCL-XL/2 proteins have similar structures and functions, which could lead to undesirable side effects because of inhibitors that can bind to both BCL-XL and BCL-2. Therefore, it is crucial to expound on the structural basis of the selective mechanism towards BCL-XL/2 inhibition.

Effect of competence health cultivation on the prevention and control of inadvertent perioperative hypothermia.

OBJECTIVE To explore the feasibility of health competence cultivation on the prevention and control of Inadvertent Perioperative Hypothermia (IPH). METHODS Patients with expected spinal surgery were divided into group A and group B by the random number method. Group B followed routine IPH management, and health training measures for performance and ability were implemented in Group A.

Structure-based virtual screening of natural products as potential stearoyl-coenzyme a desaturase 1 (SCD1) inhibitors.

Stearyl coenzyme A desaturase enzyme 1 (SCD1) is a key enzyme that catalyzes the conversion of saturated fatty acids (SFA) into monounsaturated fatty acids (MUFA) and plays a vital role in lipid metabolism of tumor cells. SCD1 is overexpressed in a variety of malignant tumors, and its related inhibitors showed significant anti-tumor activity in vitro and in vivo experiments, which is a new target for tumor therapy. The focus of this study is to identify novel SCD1 inhibitors from natural products through computer simulations.

Refined pharmacophore features for virtual screening of human thromboxane A2 receptor antagonists.

For a long time, the structural basis of TXA2 receptor is limited due to the lack of crystal structure information, till the release of the crystal structure of TXA2 receptor, which deepens our understanding about ligand recognition and selectivity mechanisms of this physiologically important receptor. In this research, we report the successful implementation in the discovery of an optimal pharmacophore model of human TXA2 receptor antagonists through virtual screening. Structure-based pharmacophore models were generated based on two crystal structures of human TXA2 receptor (PDB entry 6IIU and 6IIV).

Computational investigation of TGF-β receptor inhibitors for treatment of idiopathic pulmonary fibrosis: Field-based QSAR model and molecular dynamics simulation.

The discovery of drugs relevant to transforming growth factor β (TGF-β) receptor inhibitors have been considered as a considerable challenge during therapy idiopathic pulmonary fibrosis diseases. For the first time, herein we illustrate a field-based quantitative structure-activity relationship (QSAR) model and molecular dynamics (MD) simulations for novel 7-substituted-pyrazolo [4, 3-b] pyridine derivatives with biological activity for the TGF-β receptor, with an attempt of elucidating the 3D structural features that are essential for the activity. Results demonstrate that the field-based model (Q = 0.

Design, synthesis and biological evaluation of novel asperphenamate derivatives.

A series of novel asperphenamate derivatives were designed and synthesized, including series I (the A-phenyl group replaced with various aromatic heterocycles) and series II (the acyl group substituted by sulfonyl group). All compounds have been screened for their antiproliferative activity in vitro against MCF-7, HeLa, and BEL-7402 cell lines by the standard MTT method. Structure-activity relationship studies displayed the heterocycle type played an important role in activity.

Synthesis and cytotoxicity of novel 10-substituted dihydroartemisinin derivatives containing N-arylphenyl-ethenesulfonamide groups.

The manuscript describes the synthesis of 10-substituted dihydroartemisinin derivatives containing N-aryl phenylethenesulfonamide groups and their in vitro anti-tumor activities against the HT-29, MDA-MB-231, U87MG, H460, A549 and HL-60 cancer cell lines and the normal WI-38 cell line. Most tested compounds showed enhanced cytotoxic activities and good selectivity toward the MDA-MB-231, HT-29 and HL-60 cell lines, with IC50 values in the single-digit μM range as compared with dihydroartemisinin (DHA), and all of them displayed less toxicity towards WI-38 cells. Among them, compounds 3c and 6c with trifluoromethoxy groups on the N-phenyl ring were found to be most active compounds against the six tested cancer cell lines.

[Investigation of relationship between prehospital care for traumatic shock and postoperative acute lung injury/acute respiratory distress syndrome].

Objective: To investigate and analyze the correlation and clinical significance of prehospital treatment for traumatic shock and postoperative acute lung injury (ALI)/acute respiratory distress syndrome (ARDS).

Methods: Six hundred cases in the last 10 years were enrolled for double-blind randomized control study. They were divided into 3 groups.

[Clinical study of the effect of verapamil-procaine compound in prevention and treatment of acute respiratory distress syndrome after high risk operation].

Objective: To observe the effect of verapamil-procaine compound (V-P) on prevention and treatment of acute respiratory distress syndrome (ARDS) subsequent to high risk operation.

Methods: Altogether 150 cases of major operations with high risk of ARDS were enrolled for study. They were randomly divided into three groups.