Anticancer activity of subfractions containing pure compounds of Chaga mushroom (Inonotus obliquus) extract in human cancer cells and in Balbc/c mice bearing Sarcoma-180 cells

The Chaga mushroom (Inonotus obliquus) has been used in folk medicine to treat cancers. However, limited information exists on the underlying anticancer effects of the major component of I. obliquus in vivo. We hypothesize that the pure compounds (3β-hydroxy-lanosta-8,24-dien-21-al, inotodiol and lanosterol, respectively) separated from I. obliquus would inhibit tumor growth in Balbc/c mice bearing Sarcoma-180 cells (S-180) in vivo and growth of human carcinoma cells in vitro. To test this hypothesis, the growth inhibition of each subfraction isolated from I. obliquus on human carcinoma cell lines (lung carcinoma A-549 cells, stomach adenocarcinoma AGS cells, breast adenocarcinoma MCF-7 cells, and cervical adenocarcinoma HeLa cells) was tested in vitro. Then, after S-180 implantation, the mice were fed a normal chow supplemented with 0, 0.1 or 0.2 mg of subfraction 1, 2 or 3 per mouse per day. All of the subfractions isolated from I. obliquus showed significant cytotoxic activity against the selected cancer cell lines in vitro. Subfraction 1 was more active than subfraction 2 and subfraction 3 against the A549, AGS and MCF-7 cancer cell lines in vitro. In in vivo results, subfraction 1 isolated from I. obliquus at concentrations of 0.1 and 0.2 mg/mouse per day significantly decreased tumor volume by 23.96% and 33.71%, respectively, as compared with the control. Subfractions 2 and 3 also significantly inhibited tumor growth in mice bearing S-180 as compared with the control mouse tumor. Subfraction 1 isolated from I. obliquus showed greater inhibition of tumor growth than subfractions 2 and 3, which agrees well with the in vitro results. The results suggest that I. obliquus and its compounds in these subfractions isolated from I. obliquus could be used as natural anticancer ingredients in the food and/or pharmaceutical industry

Lubricin Surface Modification Improves Tendon Gliding After Tendon Repair in a Canine Model In Vitro

Introduction: The role of friction as a source of adhesions has been recently investigated, with data suggesting that many strong repairs also have higher friction [1], and that this higher friction is associated with poorer results, at least in animal models [2]. Lubricin is a mucinous glycoprotein responsible for the boundary lubrication of articular cartilage [3,4]. Recent studies have identified lubricin on the surface of FDP tendon [5,6] suggesting that it may play a role in tendon lubrication. Tendon surface modification with gelatin and hyaluronic acid reduces the gliding resistance of both tendon graft and repaired tendon [7][8][9]. The purpose of this study was to investigate the effects of lubricin with or without hyaluronic acid (HA) on the gliding of repaired FDP tendon in a canine model in vitro. Materials and Methods: 32 flexor digitorum profundus (FDP) tendons from the 2nd -5th digits of forepaws from 4 adult mongrel dogs were used. The dogs were sacrificed for other IACUC approved projects. In each digit the proximal and middle phalanges, FDP tendon, flexor digitorum superficialis (FDS) tendon and FDS insertion, and proximal pulley were then harvested as a unit. The proximal interphalangeal joint was fixed in full extension. A complete laceration to the FDP tendon was made 6mm distal to the proximal pulley (analogous to the A2 pulley in humans) and repaired with a modified Pennington technique. After the gliding resistance of the repaired tendon was measured in vitro, the tendons were treated with one of four solutions (n=8 per group): Saline; 10% gelatin/1% HA/1% EDC (1-ethyl-3-(3-dimethylaminopropyl) carbdiimide hydrochloride) /1% NHS (Nhydroxysuccinimde) (cd-HA-gelatin); 10% gelatin/1% EDC/1% NHS + lubricin (cd-gelatin + lubricin); 10% gelatin/1% HA/1% EDC/1% NHS+ lubricin (cd-HA-gelatin + lubricin). Lubricin was purified from bovine synovial fluid [10]. After treatment, tendon gliding resistance was measured for 1000 cycles of simulated flexion/extension tendon motion. The average and peak gliding resistance over the flexion/extension cycle were calculated and compared to baseline. Treatment groups were compared using ANOVA. Following testing, the surface of the repaired tendon and its proximal pulley was also assessed qualitatively for surface smoothness by scanning electron microscopy. Results: The increase in average and peak gliding resistance in cd-HA-gelatin, cd-gelatin+lubricin, and cd-HA-gelatin+ lubricin tendons was significantly less than that of the saline control tendons after 1000 cycles (p<0.05) Discussion: In this study, the cd-HA-gelatin, cd-gelatin+lubricin and cd-HAgelatin+lubricin all improved the gliding resistance of the repaired flexor tendon compared to the saline controls. The two lubricin treated groups had the lowest gliding resistance throughout testing. The cd-HA-gelatin+lubricin tendons were significantly lower than the tendons treated with cd-HA-gelatin alone. While not significant, there was clearly a trend for improved results with cd-gelatin+lubricin, as well. The addition of lubricin to a tendon surface pre-treated with cd-gelatin and HA significantly reduces gliding resistance and maintains a qualitatively smooth tendon and pulley surface after 1000 cycles of simulated flexion/extension tendon motion compared to the carbodiimide derivatized hyaluronic acid (cd-HA-gelatin) preparation alone. These findings may have important implications for the development of tissue engineered tendon surfaces to improve the results after tendon repair

Sonographically Guided Core Biopsy of the Breast: Comparison of 14-Gauge Automated Gun and 11-Gauge Directional Vacuum-Assisted Biopsy Methods

OBJECTIVE: To compare the outcomes of 14-gauge automated biopsy and 11-gauge vacuum-assisted biopsy for the sonographically guided core biopsies of breast lesions. MATERIALS AND METHODS: We retrospectively reviewed all sonographically guided core biopsies performed from January 2002 to February 2004. The sonographically guided core biopsies were performed with using a 14-gauge automated gun on 562 breast lesions or with using an 11-gauge vacuum-assisted device on 417 lesions. The histologic findings were compared with the surgical, imaging and follow-up findings. The histologic underestimation rate, the repeat biopsy rate and the false negative rates were compared between the two groups. RESULTS: A repeat biopsy was performed on 49 benign lesions because of the core biopsy results of the high-risk lesions (n = 24), the imaging-histologic discordance (n = 5), and the imaging findings showing disease progression (n = 20). The total underestimation rates, according to the biopsy device, were 55% (12/22) for the 14-gauge automated gun biopsies and 36% (8/22) for the 11-gauge vacuum-assisted device (p = 0.226). The atypical ductal hyperplasia (ADH) underestimation (i.e., atypical ductal hyperplasia at core biopsy and carcinoma at surgery) was 58% (7/12) for the 14-gauge automated gun biopsies and 20% (1/5) for the 11-gauge vacuum-assisted biopsies. The ductal carcinoma in situ (DCIS) underestimation rate (i.e., ductal carcinoma in situ upon core biopsy and invasive carcinoma found at surgery) was 50% (5/10) for the 14-gauge automated gun biopsies and 41% (7/17) for the 11-gauge vacuum-assisted biopsies. The repeat biopsy rates were 6% (33/562) for the 14-gauge automated gun biopsies and 3.5% (16/417) for the 11-gauge vacuum-assisted biopsies. Only 5 (0.5%) of the 979 core biopsies were believed to have missed the malignant lesions. The false-negative rate was 3% (4 of 128 cancers) for the 14-gauge automated gun biopsies and 1% (1 of 69 cancers) for the 11-gauge vacuum-assisted biopsies. CONCLUSION: The outcomes of the sonographically guided core biopsies performed with the 11-gauge vacuum-assisted device were better than those outcomes of the biopsies performed with the 14-gauge automated gun in terms of underestimation, rebiopsy and the false negative rate, although these differences were not statistically significant.This study is supported by KISTEP and the Ministry of Science and Technology, Korea

Impact of Treadmill Running and Sex on Hippocampal Neurogenesis in the Mouse Model of Amyotrophic Lateral Sclerosis

Hippocampal neurogenesis in the subgranular zone (SGZ) of dentate gyrus (DG) occurs throughout life and is regulated by pathological and physiological processes. The role of oxidative stress in hippocampal neurogenesis and its response to exercise or neurodegenerative diseases remains controversial. The present study was designed to investigate the impact of oxidative stress, treadmill exercise and sex on hippocampal neurogenesis in a murine model of heightened oxidative stress (G93A mice). G93A and wild type (WT) mice were randomized to a treadmill running (EX) or a sedentary (SED) group for 1 or 4 wk. Immunohistochemistry was used to detect bromodeoxyuridine (BrdU) labeled proliferating cells, surviving cells, and their phenotype, as well as for determination of oxidative stress (3-NT; 8-OHdG). BDNF and IGF1 mRNA expression was assessed by in situ hybridization. Results showed that: (1) G93A-SED mice had greater hippocampal neurogenesis, BDNF mRNA, and 3-NT, as compared to WT-SED mice. (2) Treadmill running promoted hippocampal neurogenesis and BDNF mRNA content and lowered DNA oxidative damage (8-OHdG) in WT mice. (3) Male G93A mice showed significantly higher cell proliferation but a lower level of survival vs. female G93A mice. We conclude that G93A mice show higher hippocampal neurogenesis, in association with higher BDNF expression, yet running did not further enhance these phenomena in G93A mice, probably due to a ‘ceiling effect’ of an already heightened basal levels of hippocampal neurogenesis and BDNF expression

Status and Prospects of ZnO-Based Resistive Switching Memory Devices

In the advancement of the semiconductor device technology, ZnO could be a prospective alternative than the other metal oxides for its versatility and huge applications in different aspects. In this review, a thorough overview on ZnO for the application of resistive switching memory (RRAM) devices has been conducted. Various efforts that have been made to investigate and modulate the switching characteristics of ZnO-based switching memory devices are discussed. The use of ZnO layer in different structure, the different types of filament formation, and the different types of switching including complementary switching are reported. By considering the huge interest of transparent devices, this review gives the concrete overview of the present status and prospects of transparent RRAM devices based on ZnO. ZnO-based RRAM can be used for flexible memory devices, which is also covered here. Another challenge in ZnO-based RRAM is that the realization of ultra-thin and low power devices. Nevertheless, ZnO not only offers decent memory properties but also has a unique potential to be used as multifunctional nonvolatile memory devices. The impact of electrode materials, metal doping, stack structures, transparency, and flexibility on resistive switching properties and switching parameters of ZnO-based resistive switching memory devices are briefly compared. This review also covers the different nanostructured-based emerging resistive switching memory devices for low power scalable devices. It may give a valuable insight on developing ZnO-based RRAM and also should encourage researchers to overcome the challenges

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field