Complex Crystal Structure Determination of Hsp90-NVP-AUY922 and Anti-NSCLC Activity of NVP-AUY922.

New targeted chemotherapy agents greatly improved five-year survival in NSCLC patients, but which were susceptible to drug resistance. NVP-AUY922, terminated in phase II clinical trials, exhibited promising anti-NSCLC (non-small-cell lung cancer) activity targeting to Hsp90 (heat shock protein), which demonstrated advantages in overcoming drug resistance as a broad-spectrum anti-cancer target. It was expected to develop novel anti-NSCLC drugs to overcome drug resistance by the structural optimization of NVP-AUY922.

Rational Design and Synthesis of 3-Morpholine Linked Aromatic-Imino-1-Indoles as Novel Kv1.5 Channel Inhibitors Sharing Vasodilation Effects.

Atrial fibrillation (AF) is the most common clinical sustained arrhythmia; clinical therapeutic drugs have low atrial selectivity and might cause more severe ventricle arrhythmias while stopping AF. As an anti-AF drug target with high selectivity on the atrial muscle cells, the undetermined crystal structure of Kv1.5 potassium channel impeded further new drug development.

Atheroprotective Effects and Molecular Mechanism of Berberine.

Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide. Atherosclerosis is the main pathological basis of cardiovascular diseases and it is closely associated with hyperlipidemia, endothelial injury, macrophage-derived foam cells formation, proliferation and migration of vascular smooth muscle cells (VSMCs), platelet aggregation, and altered gut microbiota. Various symptomatic treatments, that are currently used to inhibit atherosclerosis, need to be administered in long term and their adverse effects cannot be ignored.

Role of Long Non-coding RNAs on Bladder Cancer.

Bladder cancer (BC) is the most common malignant tumor in the urinary system, and its early diagnosis is conducive to improving clinical prognosis and prolonging overall survival time. However, few biomarkers with high sensitivity and specificity are used as diagnostic markers for BC. Multiple long non-coding RNAs (lncRNAs) are abnormally expressed in BC, and play key roles in tumorigenesis, progression and prognosis of BC.

Multiple functions of autophagy in vascular calcification.

Background: Vascular calcification is a closely linked to cardiovascular diseases, such as atherosclerosis, chronic kidney disease, diabetes, hypertension and aging. The extent of vascular calcification is closely correlate with adverse clinical events and cardiovascular all-cause mortality. The role of autophagy in vascular calcification is complex with many mechanistic unknowns.

Complex Crystal Structure Determination and Anti-non-small Cell Lung Cancer Activity of Hsp90 Inhibitor SNX-2112.

SNX-2112, as a promising anticancer lead compound targeting heat shock protein 90 (Hsp90), absence of complex crystal structure of Hsp90 -SNX-2112 hindered further structural optimization and understanding on molecular interaction mechanism. Herein, a high-resolution complex crystal structure of Hsp90 -SNX-2112 was successfully determined by X-ray diffraction, resolution limit, 2.14 Å, PDB ID 6LTK, and their molecular interaction was analyzed in detail, which suggested that SNX-2112 was well accommodated in the ATP-binding pocket to disable molecular chaperone activity of Hsp90, therefore exhibiting favorable inhibiting activity on three non-small cell lung cancer (NSCLC) cell lines (IC, 0.

Anti-NSCLC activity in vitro of Hsp90 inhibitor KW-2478 and complex crystal structure determination of Hsp90-KW-2478.

KW-2478 is a promising anti-cancer lead compound targeting to the molecular chaperone heat shock protein 90  (Hsp90). Absence of complex crystal structure of Hsp90-KW-2478, however, hampered further structure optimization of KW-2478 and understanding on the molecular interaction mechanism. Herein, a high-resolution complex crystal structure of Hsp90-KW-2478 was determined by X-ray diffraction (XRD, resolution limit: 1.

Knockdown of TRIM26 inhibits the proliferation, migration and invasion of bladder cancer cells through the Akt/GSK3β/β-catenin pathway.

Tripartite motif-containing protein 26 (TRIM26) is a member of the TRIM protein family and has been demonstrated to play crucial roles in several types of cancers. However, the biological role of TRIM26 in bladder cancer and the mechanism have not been studied. In this study, we investigated the expression of TRIM26 in bladder cancer tissues and their adjacent non-tumor tissues by Western blot and qRT-PCR.

Complex crystal structure determination and anti-non-small-cell lung cancer activity of the Hsp90 inhibitor Debio0932.

Debio0932 is a promising lead compound in phase I clinical trials targeting the N-terminal ATP-binding pocket of the molecular chaperone heat-shock protein 90 (Hsp90). The absence of a crystal structure of the Hsp90-Debio0932 complex, however, has impeded further structural optimization of Debio0932 and understanding of the molecular-interaction mechanism. Here, a high-resolution crystal structure of the Hsp90-Debio0932 complex was successfully determined (resolution limit 2.

Nϵ-Carboxymethyl-Lysine Deteriorates Vascular Calcification in Diabetic Atherosclerosis Induced by Vascular Smooth Muscle Cell-Derived Foam Cells.

Nϵ-carboxymethyl-lysine (CML), an advanced glycation end product, is involved in vascular calcification (VC) in diabetic atherosclerosis. This study aimed to investigate the effects of CML on VC in diabetic atherosclerosis induced by vascular smooth muscle cell (VSMC)-derived foam cells. Human studies, animal studies and cell studies were performed.

Localization Analysis of Heterophilic Antigen Epitopes of H1N1 Influenza Virus Hemagglutinin.

Previous studies have indicated that two monoclonal antibodies (mAbs; A1-10 and H1-84) of the hemagglutinin (HA) antigen on the H1N1 influenza virus cross-react with human brain tissue. It has been proposed that there are heterophilic epitopes between the HA protein and human brain tissue (Guo et al. in Immunobiology 220:941-946, 2015).

Research Progress on PARP14 as a Drug Target.

Poly-adenosine diphosphate-ribose polymerase (PARP) implements posttranslational mono- or poly-ADP-ribosylation modification of target proteins. Among the known 18 members in the enormous family of PARP enzymes, several investigations about PARP1, PARP2, and PARP5a/5b have been launched in the past few decades; more specifically, PARP14 is gradually emerging as a promising drug target. An intact PARP14 (also named ARTD8 or BAL2) is constructed by macro1, macro2, macro3, WWE, and the catalytic domain.

LncRNA UCA1 Promotes Mitochondrial Function of Bladder Cancer via the MiR-195/ARL2 Signaling Pathway.

Background/aims: This study aims to identify whether Urothelial Cancer Associated 1 (UCA1) regulates mitochondrial metabolic reprogramming in bladder cancer, and to explore how UCA1 participates in mitochondrial metabolism by the UCA1/miR-195/ARL2 signaling pathway; these findings may be aid in the development of tumor diagnostic and therapeutic strategies.

Methods: Bladder tissues were obtained from patients. Stable cell lines were constructed, with ectopic expression of UCA1 in UMUC2 cells and knockdown of UCA1 in 5637 cells.

[Case-control study on the iliac bone flap transplantation with deep circumflex iliac artery and quadratus femoris bone flap transplantation for the treatment of Garden III/IV femoral neck fracture of young and middle-aged patients].

Objective: To compare the clinical effects between hip anterior S-P approach combined with iliac bone flap transplantation with deep circumflex iliac artery and posterior K-L approach combined with quadratus femoris bone flap transplantation for the treatment of femoral neck fracture of Garden III-IV in young and middle-aged patients.

Methods: From January 2004 to January 2011,46 patients with femoral neck fractures were treated by two kinds of operation. Among them, 20 cases were treated with anterior S-P approach combined with iliac bone flap transplantation with deep circumflex iliac artery, included 12 males and 8 females with an average age of (32.

Long non-coding RNA UCA1 promotes glutamine metabolism by targeting miR-16 in human bladder cancer.

Objective: Long non-coding ribonucleic acid urothelial carcinoma-associated 1 has been found to be a participant in cancer development and glucose metabolism in bladder cancer. However, the role of urothelial carcinoma-associated 1 in metabolic reprogramming in cancer remains to be clarified. In this study, we aim to elucidate the molecular mechanism underlying the regulation of glutamine metabolism by urothelial carcinoma-associated 1 in bladder cancer.

[Preparation and partial characterization of monoclonal antibodies against HA protein of H1 subtype influenza virus].

Aim: Preparation of H1 subtype of influenza virus HA protein monoclonal antibody (mAbs), and to analyse their reactivity.

Methods: H1N1 influenza virus vaccine (2009) and seasonal A1 influenza virus vaccine as antigen, conventional immunization, fusion, cloning, access to the antigen-specific mAbs. To study the reactivity and specificity of mAbs by ELISA, HI test and Western blot.

[Construction and expression of recombinant adenovirus vector carrying human endostatin, K5 and endostatin-K5 gene].

Aim: To construct the recombinant adenoviral vectors expressing human endostatin, K5 and endostatin-K5 gene respectively, and study their bioactivity in vitro.

Methods: Human endostatin, K5 and endostatin-K5 gene were amplified by PCR, which were then subcloned into shuttle vector pAd5-CMV-H1H2-MCS-6His by enzyme and ligation respectively. The positive recombinant plasmids linearized by Pac I were cotransfected into HEK 293 cells with the Pac I linearized adenoviral backbone plasmid using calcium phosphate precipitation method.

[Construction of an expression vector for high expression of siRNA].

Aim: To construct the vector for efficient expression of siRNA using pre-mir30 backbone.

Methods: By chemical synthesis method, pre-mir30 backbone introduced an appropriate restriction enzyme site for foreign shRNA inserting was cloned into an expressing vector containing U6 promoter. The silencing efficiency of a new siRNA expressing vector was detected by transfection and Western blot.