Effects of Phosphodiesterase-5 Inhibitors in Patients with Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

Chronic obstructive pulmonary disease (COPD) is a major burden of healthcare worldwide. We aimed to determine the effects of PDE-5 inhibitors on clinical outcomes and haemodynamic parameters in patients with COPD. A PROSPERO-registered systematic review and meta-analysis (identification number CRD42021227578) were performed to analyse the effects of PDE-5 inhibitors in patients with COPD. Data were sourced from MEDLINE, EMBASE, Cochrane Register of Controlled Trials and "ClinicalTrials.gov." Randomised controlled trials (RCTs) comparing PDE-5 inhibitors with control in patients with COPD were included. Quality assessment was carried out using the Cochrane Collaboration's tool for assessing the risk of bias in randomised trials. The pooled mean difference of 6-minute walk distance (6MWD) and mean pulmonary arterial pressure based on inverse variance estimation were analysed with a fixed-effect model or random-effects model meta-analysis. Nine RCTs involving 414 patients were included in the review. There was no significant difference in 6MWD (mean difference = 22.06 metres, 95% confidence interval (CI), -5.80 to 49.91). However, there was a statistically significant difference between PDE-5 inhibitor and control groups in mean pulmonary artery pressure (mean difference = -3.83 mmHg, 95% CI, -5.93 to -1.74). Headaches were the most common adverse event, occurring significantly in the PDE-5 inhibitor intervention group (odds ratio 3.83, 95% CI, 1.49 to 9.86). This systematic review indicates that PDE-5 inhibitors do not improve exercise capacity despite some possible improvements in haemodynamic parameters in COPD patients

Effect of 5-aminolevulinic acid-based photodynamic therapy via reactive oxygen species in human cholangiocarcinoma cells

Cancer cells have been reported to exhibit an enhanced capacity for protoporphyrin IX (PpIX) synthesis facilitated by the administration of 5-aminolevulinic acid (ALA). We investigated the effect of ALA-based photodynamic therapy (PDT) on human cholangiocarcinoma cells (HuCC-T1). Since protoporphyrin IX (PpIX), a metabolite of ALA, can produce reactive oxygen species (ROS) under irradiation and then induce phototoxicity, ALA-based PDT is a promising candidate for the treatment of cholangiocarcinoma. When various concentrations of ALA (0.05–2 mM) were used to treat HuCC-T1 cells for 6 or 24 hours, the intracellular PpIX level increased according to the ALA concentration and treatment time. Furthermore, an increased amount of PpIX in HuCC-T1 cells induced increased production of ROS by irradiation, resulting in increased phototoxicity

Doxorubicin-incorporated polymeric micelles composed of dextran-b-poly(DL-lactide-co-glycolide) copolymer

Young-Il Jeong1,*, Do Hyung Kim1,2,*, Chung-Wook Chung1, Jin-Ju Yoo1, Kyung Ha Choi1, Cy Hyun Kim1,2, Seung Hee Ha1, Dae Hwan Kang1,2 1National Research and Development Center for Hepatobiliary Cancer, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea, Research Institute for Convergence of Biomedical Science and Technology, 2School of Medicine, Pusan National University, Yangsan, Republic of Korea*These authors contributed equally to this work.Background: Polymeric micelles using amphiphilic macromolecules are promising vehicles for antitumor targeting. In this study, we prepared anticancer agent-incorporated polymeric micelles using novel block copolymer.Methods: We synthesized a block copolymer composed of dextran and poly (DL-lactide-co-glycolide) (DexbLG) for antitumor drug delivery. Doxorubicin was selected as the anticancer drug, and was incorporated into polymeric micelles by dialysis. Polymeric micelles were observed by transmission electron microscopy to be spherical and smaller than 100 nm, with a narrow size distribution. The particle size of doxorubicin-incorporated polymeric micelles increased with increasing drug content. Higher initial drug feeding also increased the drug content. Results: During the drug-release study, an initial burst release of doxorubicin was observed for 10 hours, and doxorubicin was continuously released over 4 days. To investigate the in vitro anticancer effects of the polymeric micelles, doxorubicin-resistant HuCC-T1 cells were treated with a very high concentration of doxorubicin. In an antiproliferation study, the polymeric micelles showed higher cytotoxicity to doxorubicin-resistant HuCC-T1 cells than free doxorubicin, indicating that the polymeric micelles were effectively engulfed by tumor cells, while free doxorubicin hardly penetrated the tumor cell membrane. On confocal laser scanning microscopy, free doxorubicin expressed very weak fluorescence intensity, while the polymeric micelles expressed strong red fluorescence. Furthermore, in flow cytometric analysis, fluorescence intensity of polymeric micelles was almost twice as high than with free doxorubicin.Conclusion: DexbLG polymeric micelles incorporating doxorubicin are promising vehicles for antitumor drug targeting.Keywords: dextran, polymeric micelle, block copolymer, poly(DL-lactide-co-glycolide

B Cells Regulate Neutrophilia during Mycobacterium tuberculosis Infection and BCG Vaccination by Modulating the Interleukin-17 Response

We have previously demonstrated that B cells can shape the immune response to Mycobacterium tuberculosis, including the level of neutrophil infiltration and granulomatous inflammation at the site of infection. The present study examined the mechanisms by which B cells regulate the host neutrophilic response upon exposure to mycobacteria and how neutrophilia may influence vaccine efficacy. To address these questions, a murine aerosol infection tuberculosis (TB) model and an intradermal (ID) ear BCG immunization mouse model, involving both the μMT strain and B cell-depleted C57BL/6 mice, were used. IL (interleukin)-17 neutralization and neutrophil depletion experiments using these systems provide evidence that B cells can regulate neutrophilia by modulating the IL-17 response during M. tuberculosis infection and BCG immunization. Exuberant neutrophilia at the site of immunization in B cell-deficient mice adversely affects dendritic cell (DC) migration to the draining lymph nodes and attenuates the development of the vaccine-induced Th1 response. The results suggest that B cells are required for the development of optimal protective anti-TB immunity upon BCG vaccination by regulating the IL-17/neutrophilic response. Administration of sera derived from M. tuberculosis-infected C57BL/6 wild-type mice reverses the lung neutrophilia phenotype in tuberculous μMT mice. Together, these observations provide insight into the mechanisms by which B cells and humoral immunity modulate vaccine-induced Th1 response and regulate neutrophila during M. tuberculosis infection and BCG immunization. © 2013 Kozakiewicz et al

Clinical Implication of Targeting of Cancer Stem Cells

The existence of cancer stem cells (CSCs) is receiving increasing interest particularly due to its potential ability to enter clinical routine. Rapid advances in the CSC field have provided evidence for the development of more reliable anticancer therapies in the future. CSCs typically only constitute a small fraction of the total tumor burden; however, they harbor self-renewal capacity and appear to be relatively resistant to conventional therapies. Recent therapeutic approaches aim to eliminate or differentiate CSCs or to disrupt the niches in which they reside. Better understanding of the biological characteristics of CSCs as well as improved preclinical and clinical trials targeting CSCs may revolutionize the treatment of many cancers. Copyright (c) 2012 S. Karger AG, Base

Prevalence, sources, and predictors of soy consumption in breast cancer

<p>Abstract</p> <p>Background</p> <p>A number of components in soy appear to have anticancer properties, including the isoflavones, genistein and daidzein. The use of soy by women with breast cancer is now being questioned because of the estrogen-like effects of isoflavones and possible interactions with tamoxifen. Clinicians providing nutrition counseling to these women are concerned because the availability of soy foods has increased dramatically in the past few years. The goal of this study was to quantify the intake of isoflavones in women with breast cancer.</p> <p>Methods</p> <p>A cross-sectional study of 100 women with breast cancer treated at Cancer Treatment Centers of America^®between 09/03 and 02/04. Each patient completed a soy food frequency questionnaire (FFQ) that was scored by Fred Hutchinson Cancer Research Center. Demographic and clinical predictors of soy intake were evaluated using one-way non-parametric Mann Whitney test and non-parametric spearman's rank correlation.</p> <p>Results</p> <p>Mean age was 50.5 years (std. dev. = 9.4; range 31–70) and mean BMI was 27.3 kg/m²(std. dev. = 6.75; range 17–59). Genistein and Daidzein consumption was limited to 65 patients with a mean intake of 11.6 mg/day (std. dev. = 21.9; range 0–97.4) and 7.6 mg/day (std. dev. = 14.1; range 0–68.9) respectively. Soy milk (37%) and pills containing soy, isoflavones, or "natural" estrogen (24%) were the two biggest contributors to isoflavone intake.</p> <p>Conclusion</p> <p>Our study suggests that the isoflavone intake of breast cancer patients at our hospital was quite variable. Thirty-five patients reported no soy intake. The mean daily intake of 11.6 mg genistein and 7.4 mg daidzein, is the equivalent of less than 1/4 cup of tofu per day. This amount is higher than what has been previously reported in non-Asian American women.</p

Thermal Properties of Graphene, Carbon Nanotubes and Nanostructured Carbon Materials

Recent years witnessed a rapid growth of interest of scientific and engineering communities to thermal properties of materials. Carbon allotropes and derivatives occupy a unique place in terms of their ability to conduct heat. The room-temperature thermal conductivity of carbon materials span an extraordinary large range - of over five orders of magnitude - from the lowest in amorphous carbons to the highest in graphene and carbon nanotubes. I review thermal and thermoelectric properties of carbon materials focusing on recent results for graphene, carbon nanotubes and nanostructured carbon materials with different degrees of disorder. A special attention is given to the unusual size dependence of heat conduction in two-dimensional crystals and, specifically, in graphene. I also describe prospects of applications of graphene and carbon materials for thermal management of electronics.Comment: Review Paper; 37 manuscript pages; 4 figures and 2 boxe

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Host factors do not influence the colonization or infection by fluconazole resistant Candida species in hospitalized patients

Nosocomial yeast infections have significantly increased during the past two decades in industrialized countries, including Taiwan. This has been associated with the emergence of resistance to fluconazole and other antifungal drugs. The medical records of 88 patients, colonized or infected with Candida species, from nine of the 22 hospitals that provided clinical isolates to the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) program in 1999 were reviewed. A total of 35 patients contributed fluconazole resistant strains [minimum inhibitory concentrations (MICs) ≧ 64 mg/l], while the remaining 53 patients contributed susceptible ones (MICs ≦ 8 mg/l). Fluconazole resistance was more frequent among isolates of Candida tropicalis (46.5%) than either C. albicans (36.8%) or C. glabrata (30.8%). There was no significant difference in demographic characteristics or underlying diseases among patients contributing strains different in drug susceptibility