High Smac/DIABLO expression is associated with early local recurrence of cervical cancer

<p>Abstract</p> <p>Background</p> <p>In a recent pilot report, we showed that Smac/DIABLO mRNA is expressed <it>de novo </it>in a subset of cervical cancer patients. We have now expanded this study and analyzed Smac/DIABLO expression in the primary lesions in 109 cervical cancer patients.</p> <p>Methods</p> <p>We used immunohistochemistry of formalin-fixed, paraffin-embedded tissue sections to analyze Smac/DIABLO expression in the 109 primary lesions. Seventy-eight samples corresponded to epidermoid cervical cancer and 31 to cervical adenocarcinoma. The median follow up was 46.86 months (range 10–186).</p> <p>Results</p> <p>Smac/DIABLO was expressed in more adenocarcinoma samples than squamous tumours (71% vs 50%; p = 0.037). Among the pathological variables, a positive correlation was found between Smac/DIABLO immunoreactivity and microvascular density, a marker for angiogenesis (p = 0.04). Most importantly, Smac/DIABLO immunoreactivity was associated with a higher rate of local recurrence in squamous cell carcinoma (p = 0.002, log rank test). No association was found between Smac/DIABLO and survival rates.</p> <p>Conclusion</p> <p>Smac/DIABLO expression is a potential marker for local recurrence in cervical squamous cell carcinoma patients.</p

Yb- and Er-doped fiber laser Q-switched with an optically uniform, broadband WS2 saturable absorber.

We demonstrate a ytterbium (Yb) and an erbium (Er)-doped fiber laser Q-switched by a solution processed, optically uniform, few-layer tungsten disulfide saturable absorber (WS2-SA). Nonlinear optical absorption of the WS2-SA in the sub-bandgap region, attributed to the edge-induced states, is characterized by 3.1% and 4.9% modulation depths with 1.38 and 3.83 MW/cm(2) saturation intensities at 1030 and 1558 nm, respectively. By integrating the optically uniform WS2-SA in the Yb- and Er-doped laser cavities, we obtain self-starting Q-switched pulses with microsecond duration and kilohertz repetition rates at 1030 and 1558 nm. Our work demonstrates broadband sub-bandgap saturable absorption of a single, solution processed WS2-SA, providing new potential efficacy for WS2 in ultrafast photonic applications.The authors thank E. J. R. Kelleher for valuable discussions. MZ acknowledges support from Beihang University, China, through a Zhuoyue Bairen Program and TH from the Royal Academy of Engineering through a fellowship (Graphlex). This work at Beihang University was supported by 973 Program (2012CB315601), NSFC (61221061/61435002) and the Fundamental Research Funds for the Central Universities.This is the final version of the article. It was first available from NPG via http://dx.doi.org/10.1038/srep1748

Drugs and herbs given to prevent hepatotoxicity of tuberculosis therapy: systematic review of ingredients and evaluation studies

Background: Drugs to protect the liver are frequently prescribed in some countries as part of treatment for tuberculosis. The biological rationale is not clear, they are expensive and may do harm. We conducted a systematic review to a) describe the ingredients of "liver protection drugs"; and b) compare the evidence base for the policy against international standards. Methods: We searched international medical databases (MEDLINE, EMBASE, LILACS, CINAHL, Cochrane Central Register of Controlled Trials, and the specialised register of the Cochrane Infectious Diseases Group) and Chinese language databases (CNKI, VIP and WanFang) to April 2007. Our inclusion criteria were research papers that reported evaluating any liver protection drug or drugs for preventing liver damage in people taking anti-tuberculosis treatment. Two authors independently categorised and extracted data, and appraised the stated methods of evaluating their effectiveness. Results: Eighty five research articles met our inclusion criteria, carried out in China (77), India (2), Russia (4), Ukraine (2). These articles evaluated 30 distinct types of liver protection compounds categorised as herbal preparations, manufactured herbal products, combinations of vitamins and other non-herbal substances and manufactured pharmaceutical preparations. Critical appraisal of these articles showed that all were small, poorly conducted studies, measuring intermediate outcomes. Four trials that were described as randomised controlled trials were small, had short follow up, and did not meet international standards. Conclusion: There is no reliable evidence to support prescription of drugs or herbs to prevent liver damage in people on tuberculosis treatment

Direct Measurement of B(D0->phiX0) and B(D+->phiX+)

The first measurement of B(0->phi X0) and an upper limit for B(D+->phi X+) are determined from 22.3 pb-1 of e+e- annihilation data at a C. M. energy of 4.03 GeV. The data were recorded by the Beijing Spectrometer (BES) at BEPC. A recoil charge method is applied for the first time to charm threshold data to determine the charge of the D meson in the recoil from 9054+-309+-416 reconstructed D0, D+ mesons. The branching fractions B(D->phiX0) =(1.71+0.76-0.71+-0.17)%, and B(D+->phiX+) <1.8% are determined from 10 events with a reconstructed D and a recoiling phi. In addition, a 90% C.L. upper limit of B(D+->phi e+X0)<1.6% is determined from a search for semileptonic decays of the D+.Comment: Submitted to Phys. Rev.

Liquid exfoliation of solvent-stabilized few-layer black phosphorus for applications beyond electronics

Few-layer black phosphorus (BP) is a new two-dimensional material which is of great interest for applications, mainly in electronics. However, its lack of environmental stability severely limits its synthesis and processing. Here we demonstrate that high-quality, few-layer BP nanosheets, with controllable size and observable photoluminescence, can be produced in large quantities by liquid phase exfoliation under ambient conditions in solvents such as N-cyclohexyl-2-pyrrolidone (CHP). Nanosheets are surprisingly stable in CHP, probably due to the solvation shell protecting the nanosheets from reacting with water or oxygen. Experiments, supported by simulations, show reactions to occur only at the nanosheet edge, with the rate and extent of the reaction dependent on the water/oxygen content. We demonstrate that liquid-exfoliated BP nanosheets are potentially useful in a range of applications from ultrafast saturable absorbers to gas sensors to fillers for composite reinforcement

Receptor-targeted liposome-peptide-siRNA nanoparticles represent a novel and efficient therapeutic approach to prevent conjunctival fibrosis.

There is increasing evidence that the Myocardin-related transcription factor/Serum response factor (MRTF/SRF) pathway plays a key role in fibroblast activation and that knocking down MRTF can lead to reduced scarring and fibrosis. Here, we have developed a receptor-targeted liposome-peptide-siRNA nanoparticle as a non-viral delivery system for MRTF-B siRNA in conjunctival fibrosis. Using 50 nM siRNA, the MRTF-B gene was efficiently silenced by 76% and 72% with LYR and LER nanoparticles, respectively. The silencing efficiency was low when non-targeting peptides or siRNA alone or liposome-siRNA alone were used. LYR and LER nanoparticles also showed higher silencing efficiency than PEGylated LYR-P and LER-P nanoparticles. The nanoparticles were not cytotoxic using different liposomes, targeting peptides, and 50 nM siRNA. Three-dimensional fibroblast-populated collagen matrices were also used as a functional assay to measure contraction in vitro, and showed that MRTF-B LYR nanoparticles completely blocked matrix contraction after a single transfection treatment. In conclusion, this is the first study to develop and show that receptor-targeted liposome-peptide-siRNA nanoparticles represent an efficient and safe non-viral siRNA delivery system that could be used to prevent fibrosis after glaucoma filtration surgery and other contractile scarring conditions in the eye

Novel Inhibitor Design for Hemagglutinin against H1N1 Influenza Virus by Core Hopping Method

The worldwide spread of H1N1 avian influenza and the increasing reports about its resistance to the current drugs have made a high priority for developing new anti-influenza drugs. Owing to its unique function in assisting viruses to bind the cellular surface, a key step for them to subsequently penetrate into the infected cell, hemagglutinin (HA) has become one of the main targets for drug design against influenza virus. To develop potent HA inhibitors, the ZINC fragment database was searched for finding the optimal compound with the core hopping technique. As a result, the Neo6 compound was obtained. It has been shown through the subsequent molecular docking studies and molecular dynamic simulations that Neo6 not only assumes more favorable conformation at the binding pocket of HA but also has stronger binding interaction with its receptor. Accordingly, Neo6 may become a promising candidate for developing new and more powerful drugs for treating influenza. Or at the very least, the findings reported here may provide useful insights to stimulate new strategy in this area

Genetic Polymorphisms in CYP2E1: Association with Schizophrenia Susceptibility and Risperidone Response in the Chinese Han Population

CYP2E1 is a member of the cytochrome P450 superfamily, which is involved in the metabolism and activation of both endobiotics and xenobiotics. The genetic polymorphisms of CYP2E1 gene (Chromosome 10q26.3, Accession Number NC_000010.10) are reported to be related to the development of several mental diseases and to be involved in the clinical efficacy of some psychiatric medications. We investigated the possible association of CYP2E1 polymorphisms with susceptibility to schizophrenia in the Chinese Han Population as well as the relationship with response to risperidone in schizophrenia patients.In a case-control study, we identified 11 polymorphisms in the 5' flanking region of CYP2E1 in 228 schizophrenia patients and 384 healthy controls of Chinese Han origin. From among the cases, we chose 130 patients who had undergone 8 weeks of risperidone monotherapy to examine the relationship between their response to risperidone and CYP2E1 polymorphisms. Clinical efficacy was assessed using the Brief Psychiatric Rating Scale (BPRS).Statistically significant differences in allele or genotype frequencies were found between cases and controls at rs8192766 (genotype p = 0.0048, permutation p = 0.0483) and rs2070673 (allele: p = 0.0018, permutation p = 0.0199, OR = 1.4528 95%CI = 1.1487-1.8374; genotype: p = 0.0020, permutation p = 0.0225). In addition, a GTCAC haplotype containing 5 SNPs (rs3813867, rs2031920, rs2031921, rs3813870 and rs2031922) was observed to be significantly associated with schizophrenia (p = 7.47E-12, permutation p<0.0001). However, no association was found between CYP2E1 polymorphisms/haplotypes and risperidone response.Our results suggest that CYP2E1 may be a potential risk gene for schizophrenia in the Chinese Han population. However, polymorphisms of the CYP2E1 gene may not contribute significantly to individual differences in the therapeutic efficacy of risperidone. Further studies in larger groups are warranted to confirm our results