Effect of CYP2C9*3 gene polymorphism on lipid-lowering efficacy of fluvastatin in a Chinese hyperlipidemic population

Purpose: To investigate the frequency of gene CYP2C9*3 in Chinese populations, and to analyze the impact of CYP2C9*3 genetic polymorphism on the cholesterol-lowering effect of fluvastatin in a Chinese hyperlipidemic population.Methods: CYP2C9 genotype was determined by polymerase chain reaction - restriction fragment length polymorphism (PCR - RFLP) in 270 unrelated hyperlipidemic patients who were treated with 80mg fluvastatin monotherapy daily for 4 weeks and 250 healthy controls. Clinical data were collected prior to treatment with fluvastatin and 4 weeks after.Results: In 270 hyperlipidemic patients, the frequency of CYP2C9*3 was 3.70 % which is significantly higher than in 250 healthy controls (2.60 %) (p < 0.01). After oral intake of fluvastatin 80 mg daily for 4 weeks, CYP2C9*1/*3 genotype was associated with a decrease in LDL-C levels (by 33.9 % in CYP2C9*1/*3 versus 24.5 % for CYP2C9*1/*1, p < 0.05) and with reduction of TC (by 36.4 % in CYP2C9*1/*3 versus 19.4 % in CYP2C9*1/*1, p < 0.05).Conclusion: The frequency of CYP2C9*3 is 3.17 % in Chinese populations, and those who carry CYP2C9*3 mutation have a high risk of hyperlipidemia. CYP2C9*3 seems to increase the lipid-lowering effects of fluvastatin.Keywords: Hyperlipidemia, Gene, CYP2C9, Polymorphism, Polymerase chain reaction, Restriction fragment length polymorphism, Fluvastati

Identification of FKBP10 prognostic value in lung adenocarcinoma patients with surgical resection of brain metastases: A retrospective single-institution cohort study

Objective: To explore the expression levels and clinical value of FKBP10 in lung adenocarcinoma brain metastases. Design: A retrospective single-institution cohort study. Patients: The perioperative records of 71 patients with lung adenocarcinoma brain metastases who underwent surgical resection at the authors’ institution between November 2012 and June 2019 were retrospectively analyzed. Methods: The authors evaluated FKBP10 expression levels using immunohistochemistry in tissue arrays of these patients. Kaplan-Meier survival curves were constructed, and a Cox proportional hazards regression model was used to identify independent prognostic biomarkers. A public database was used to detect FKBP10 expression and its clinical value in primary lung adenocarcinoma. Results: The authors found that the FKBP10 protein was selectively expressed in lung adenocarcinoma brain metastases. Survival analysis showed that FKBP10 expression (p = 0.02, HR = 2.472, 95% CI [1.156, 5.289]), target therapy (p < 0.01, HR = 0.186, 95% CI [0.073, 0.477]), and radiotherapy (p = 0.006, HR = 0.330, 95% CI [0.149, 0.731]) were independent prognostic factors for survival in lung adenocarcinoma patients with brain metastases. The authors also detected FKBP10 expression in primary lung adenocarcinoma using a public database, found that FKBP10 is also selectively expressed in primary lung adenocarcinoma, and affects the overall survival and disease-free survival of patients. Limitations: The number of enrolled patients was relatively small and patients’ treatment options varied. Conclusions: A combination of surgical resection, adjuvant radiotherapy, and precise target therapy may benefit the survival of selected patients with lung adenocarcinoma brain metastases. FKBP10 is a novel biomarker for lung adenocarcinoma brain metastases, which is closely associated with survival time and may serve as a potential therapeutic target

1,3,5-Tris{[3-(1H-benzotriazol-1-ylmeth­yl)phen­oxy]meth­yl}-2,4,6-trimethyl­benzene

In the title compound, C51H45N9O3, three 1-(1H-benzotriazol-1-ylmeth­yl)-3-phen­yloxy (bmph) ligands are bonded to the central benzene ring in an asymmetric arrangement, two bmph located on one side of the central benzene ring and the other bmph located on the opposite side of the central benzene ring. The dihedral angles between the central benzene ring and the three pendant phenoxy rings are 76.71 (14), 67.81 (13) and 70.67 (16)°. In the crystal structure, one bmph is disordered over two sites in a 0.611 (5):0.389 (5) ratio. Some of the methyl H atoms are equally disordered over two sets of sites. Inter­molecular C—H⋯N hydrogen bonding is present in the crystal structure

VHZ is a novel centrosomal phosphatase associated with cell growth and human primary cancers

<p>Abstract</p> <p>Background</p> <p>VHZ is a VH1-like (member Z) dual specific protein phosphatase encoded by DUSP23 gene. Some of the dual specific protein phosphatases (DSPs) play an important role in cell cycle control and have shown to be associated with carcinogenesis. Here, the expression of VHZ associated with cell growth and human cancers was investigated.</p> <p>Results</p> <p>We generated a mouse monoclonal antibody (mAb clone#209) and rabbit polyclonal antibodies (rAb) against VHZ. We performed cell proliferation assay to learn how VHZ is associated with cell cycle by retroviral transduction to express VHZ, VHZ(C95S), and control vector in MCF-7 cells. Overexpression of VHZ [but not VHZ(C95S)] in MCF-7 cells promoted cell proliferation compared to control cells. shRNA-mediated knockdown of VHZ in MCF-7 cells showed that reduction of VHZ resulted in increased G1 but decreased S phase cell populations. Using indirect immunofluorescence, we showed that both exogenous and endogenous VHZ protein was localized at the centrosome in addition to its cytoplasmic distribution. Furthermore, using immunohistochemistry, we revealed that VHZ protein was overexpressed either in enlarged centrosomes (VHZ-centrosomal-stain) of some invasive ductal carcinomas (IDC) Stage I (8/65 cases) or in entire cytoplasm (VHZ-cytosol-stain) of invasive epithelia of some IDC Stage II/III (11/47 cases) of breast cancers examined. More importantly, upregulation of VHZ protein is also associated with numerous types of human cancer, in particular breast cancer. VHZ mAb may be useful as a reagent in clinical diagnosis for assessing VHZ positive tumors.</p> <p>Conclusions</p> <p>We generated a VHZ-specific mAb to reveal that VHZ has a novel subcellular localization, namely the centrosome. VHZ is able to facilitate G1/S cell cycle transition in a PTP activity-dependent manner. The upregulation of its protein levels in primary human cancers supports the clinical relevance of the protein in cancers.</p

Microscale intrinsic properties of hybrid unidirectional/woven composite laminates: Part I experimental tests

Understanding of the failure of composites is critical for evaluating their safety and reliability when they are in service. In this research, a combined image analysis technique using computed microtomography (micro-CT) and scanning electron microscopy (SEM) is proposed to study the microstructures, damage and failure of a hybrid unidirectional/woven composite laminate (HUWCL). Micro-CT is used to extract the 3D microscale morphology and identify the internal failure behaviours of the HUWCL. A series of material parameters, such as fiber volume fraction, void ratio and layer mode, are acquired by the statistical analysis of the micro-CT images. In addition, microscale surface damage and failure mechanism of woven and unidirectional (UD) laminae are further investigated by SEM. It is found that the matrix damage around the interface always occurs in both woven and unidirectional (UD) laminae, and distinct delamination is found between the UD laminae and the woven composites. The study shows a great potential of combining micro-CT with SEM in revealing the local damage and intrinsic failure mechanism in HUWCLs at microscale

Metropolitan all-pass and inter-city quantum communication network

We have demonstrated a metropolitan all-pass quantum communication network in field fiber for four nodes. Any two nodes of them can be connected in the network to perform quantum key distribution (QKD). An optical switching module is presented that enables arbitrary 2-connectivity among output ports. Integrated QKD terminals are worked out, which can operate either as a transmitter, a receiver, or even both at the same time. Furthermore, an additional link in another city of 60 km fiber (up to 130 km) is seamless integrated into this network based on a trusted relay architecture. On all the links, we have implemented protocol of decoy state scheme. All of necessary electrical hardware, synchronization, feedback control, network software, execution of QKD protocols are made by tailored designing, which allow a completely automatical and stable running. Our system has been put into operation in Hefei in August 2009, and publicly demonstrated during an evaluation conference on quantum network organized by the Chinese Academy of Sciences on August 29, 2009. Real-time voice telephone with one-time pad encoding between any two of the five nodes (four all-pass nodes plus one additional node through relay) is successfully established in the network within 60km.Comment: 9 pages, 2 figures, 2 table

Production and Radioprotective Effects of Pyrroloquinoline Quinone

Pyrroloquinoline quinone (PQQ) was produced by fermentation of the Methylovorus sp. MP688 strain and purified by ion-exchange chromatography, crystallization and recrystallization. The yield of PQQ reached approximately 125 mg/L and highly pure PQQ was obtained. To determine the optimum dose of PQQ for radioprotection, three doses (2 mg/kg, 4 mg/kg, 8 mg/kg) of PQQ were orally administrated to the experimental animals subjected to a lethal dose of 8.0 Gy in survival test. Survival of mice in the irradiation + PQQ (4 mg/kg) group was found to be significantly higher in comparison with the irradiation and irradiation + nilestriol (10 mg/kg) groups. The numbers of hematocytes and bone marrow cells were measured for 21 days after sublethal 4 Gy gamma-ray irradiation with per os of 4 mg/kg of PQQ. The recovery of white blood cells, reticulocytes and bone marrow cells in the irradiation + PQQ group was faster than that in the irradiation group. Furthermore, the recovery of bone marrow cell in the irradiation + PQQ group was superior to that in irradiation + nilestriol group. Our results clearly indicate favourable effects on survival under higher lethal radiation doses and the ability of pyrroloquinoline quinine to enhance haemopoietic recovery after sublethal radiation exposure

Comparison Study of Gold Nanohexapods, Nanorods, and Nanocages for Photothermal Cancer Treatment

Gold nanohexapods represent a novel class of optically tunable nanostructures consisting of an octahedral core and six arms grown on its vertices. By controlling the length of the arms, their localized surface plasmon resonance peaks could be tuned from the visible to the near-infrared region for deep penetration of light into soft tissues. Herein we compare the in vitro and in vivo capabilities of Au nanohexapods as photothermal transducers for theranostic applications by benchmarking against those of Au nanorods and nanocages. While all these Au nanostructures could absorb and convert near-infrared light into heat, Au nanohexapods exhibited the highest cellular uptake and the lowest cytotoxicity in vitro for both the as-prepared and PEGylated nanostructures. In vivo pharmacokinetic studies showed that the PEGylated Au nanohexapods had significant blood circulation and tumor accumulation in a mouse breast cancer model. Following photothermal treatment, substantial heat was produced in situ and the tumor metabolism was greatly reduced for all these Au nanostructures, as determined with ^(18)F-flourodeoxyglucose positron emission tomography/computed tomography (^(18)F-FDG PET/CT). Combined together, we can conclude that Au nanohexapods are promising candidates for cancer theranostics in terms of both photothermal destruction and contrast-enhanced diagnosis