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1.
Article in English | MEDLINE | ID: mdl-36294090

ABSTRACT

BACKGROUND: Physical activity (PA) is recommended in the management of patients with pulmonary fibrosis (PF) to improve health outcomes. Dance is one such form of PA which is meaningful, valuable, enjoyable and has demonstrated positive physical and mental health effects. METHODS: With pre-post design, 16 patients, members of the Irish Lung Fibrosis Association, were enrolled in this study. Once weekly, 75-min dance sessions were delivered for eight weeks via Zoom by an experienced choreographer. Participants completed Chronic Respiratory Questionnaire Self-Administered Standardised Format (CRQ-SAS) and European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L) to assess self-rated quality of life. A paired-sample t-test was employed to assess the mean differences between the pre-and post-intervention scores. RESULTS: Most patients (78.57%) were aged over 60 years; with 71.43% diagnosed with pulmonary fibrosis more than 3 years ago. We performed an analysis of 10/16 participants who completed the intervention (5 males, 5 females). On CRQ-SAS scale we found, (a) dyspnoea-small to moderate magnitude improvement of 0.5-1.0 among 50%, (b) fatigue-small to moderate magnitude improvement of 0.5-1.0 among 40%, (c) emotional function-small to high magnitude improvement of 0.5-2.0 among 50%, (d) mastery-small magnitude improvement of 0.5 among 20%. Participants reported their health moderate to best on Visual Analogue Scale of EQ-5D-3L which improved by 1-3 scale among 40%. Mental health improved as percentage of not feeling anxious or depressed rose post event from 42.86% to 72.73%. CONCLUSION: Our findings demonstrate that a virtual dance intervention is acceptable, enjoyable and feasible for improving health outcomes among PF patients. More organised and continuous events in future may reveal cost-benefit ratio and impact on health outcomes.


Subject(s)
Dancing , Pulmonary Fibrosis , Male , Female , Humans , Middle Aged , Aged , Dancing/psychology , Feasibility Studies , Quality of Life , Surveys and Questionnaires
2.
Article in English | MEDLINE | ID: mdl-36078841

ABSTRACT

Dance has been highlighted as one of the most enjoyable, safe, and feasible forms of physical activity, improving physical health, mental health, and general well-being, among various patients. Little is known about the effect and impact of dance interventions to improve health among patients with pulmonary diseases, and research lacks a robust synthesis of evidence. Therefore, this systematic review aimed to investigate the impact of dance intervention on patients with noninfectious pulmonary diseases. Following the PRISMA guidelines, six electronic databases were searched in May 2022. Of the 1308 unique records identified, seven studies (five quantitative, two qualitative) across four countries were included in this systematic review. Six studies investigated adult populations, and one study explored the effect of dance on children. The dance interventions lasted between 1 and 10 weeks. Overall, dance was perceived to have a broad range of physical/mental/social benefits, including quality of life, social cohesion, dyspnoea levels, balance, exercise tolerance, general well-being, and adherence to nutrition regimens. Furthermore, the dance session was the most enjoyable activity among children and adolescents with asthma. With available evidence, dance interventions are promising and may effectively improve health and well-being among patients with noninfectious pulmonary diseases. More organised and continuous long-term dance interventions in future may reveal a detailed impact on health outcomes.


Subject(s)
Lung Diseases , Quality of Life , Adolescent , Adult , Child , Exercise , Humans , Lung Diseases/therapy , Mental Health
3.
Article in English | MEDLINE | ID: mdl-34360142

ABSTRACT

Workplaces can be high-risk environments for SARS-CoV-2 outbreaks and subsequent community transmission. Identifying, understanding, and implementing effective workplace SARS-CoV-2 infection prevention and control (IPC) measures is critical to protect workers, their families, and communities. A rapid review and meta-analysis were conducted to synthesize evidence assessing the effectiveness of COVID-19 IPC measures implemented in global workplace settings through April 2021. Medline, Embase, PubMed, and Cochrane Library were searched for studies that quantitatively assessed the effectiveness of workplace COVID-19 IPC measures. The included studies comprised varying empirical designs and occupational settings. Measures of interest included surveillance measures, outbreak investigations, environmental adjustments, personal protective equipment (PPE), changes in work arrangements, and worker education. Sixty-one studies from healthcare, nursing home, meatpacking, manufacturing, and office settings were included, accounting for ~280,000 employees based in Europe, Asia, and North America. Meta-analyses showed that combined IPC measures resulted in lower employee COVID-19 positivity rates (0.2% positivity; 95% CI 0-0.4%) than single measures such as asymptomatic PCR testing (1.7%; 95% CI 0.9-2.9%) and universal masking (24%; 95% CI 3.4-55.5%). Modelling studies showed that combinations of (i) timely and widespread contact tracing and case isolation, (ii) facilitating smaller worker cohorts, and (iii) effective use of PPE can reduce workplace transmission. Comprehensive COVID-19 IPC measures incorporating swift contact tracing and case isolation, PPE, and facility zoning can effectively prevent workplace outbreaks. Masking alone should not be considered sufficient protection from SARS-CoV-2 outbreaks in the workplace.


Subject(s)
COVID-19 , Workplace , Contact Tracing , Health Personnel , Humans , Personal Protective Equipment , SARS-CoV-2
4.
Hepatol Commun ; 3(6): 748-762, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31168510

ABSTRACT

Nonalcoholic fatty liver disease is currently the most common liver disease and is a leading cause of liver-related morbidity and mortality. However, its pathogenesis remains largely unclear. We previously showed that mice deficient in mitogen-activated protein kinase (MAPK) phosphatase 5 (MKP5) spontaneously developed insulin resistance and glucose intolerance, which are associated with visceral obesity and adipose tissue inflammation. In this study, we discovered that mice deficient in MKP5 developed more severe hepatic steatosis and steatohepatitis with age or with feeding on a high-fat diet (HFD) compared to wild-type (WT) mice, and this was associated with increased expression of proinflammatory cytokines and collagen genes. Increased p38 activation in MKP5 knockout (KO) liver compared to that in WT liver was detected, which contributed to increased expression of lipid droplet-associated protein cell death-inducing DFF45-like effector A (CIDEA) and CIDEC/fat-specific protein 27 but not CIDEB through activating transcription factor 2 (ATF2). In addition, MKP5 KO liver had higher peroxisome proliferator-activated receptor gamma (PPARγ) expression compared with WT liver. On the other hand, overexpression of MKP5 or inhibition of p38 activation in hepatocytes resulted in reduced expression of PPARγ. Inhibition of p38 resulted in alleviation of hepatic steatosis in KO liver in response to HFD feeding, and this was associated with reduced expression of CIDEA, CIDEC, and proinflammatory cytokines. Conclusion: MKP5 prevents the development of nonalcoholic steatohepatitis by suppressing p38-ATF2 and p38-PPARγ to reduce hepatic lipid accumulation, inflammation, and fibrosis.

5.
PLoS One ; 12(4): e0175886, 2017.
Article in English | MEDLINE | ID: mdl-28423018

ABSTRACT

Enterococcus faecalis is a Gram-positive, opportunistic, pathogenic bacterium that causes a significant number of antibiotic-resistant infections in hospitalized patients. The development of antibiotic resistance in hospital-associated pathogens is a formidable public health threat. In E. faecalis and other Gram-positive pathogens, correlations exist between lipid composition and antibiotic resistance. Resistance to the last-resort antibiotic daptomycin is accompanied by a decrease in phosphatidylglycerol (PG) levels, whereas multiple peptide resistance factor (MprF) converts anionic PG into cationic lysyl-PG via a trans-esterification reaction, providing resistance to cationic antimicrobial peptides. Unlike previous studies that relied on thin layer chromatography and spectrophotometry, we have performed liquid chromatography-tandem mass spectrometry (LC-MS/MS) directly on lipids extracted from E. faecalis, and quantified the phospholipids through multiple reaction monitoring (MRM). In the daptomycin-sensitive E. faecalis strain OG1RF, we have identified 17 PGs, 8 lysyl-PGs (LPGs), 23 cardiolipins (CL), 3 glycerophospho-diglucosyl-diacylglycerols (GPDGDAG), 5 diglucosyl-diacylglycerols (DGDAG), 3 diacylglycerols (DAGs), and 4 triacylglycerols (TAGs). We have quantified PG and shown that PG levels vary during growth of E. faecalis in vitro. We also show that two daptomycin-resistant (DapR) strains of E. faecalis have substantially lower levels of PG and LPG levels. Since LPG levels in these strains are lower, daptomycin resistance is likely due to the reduction in PG. This lipidome map is the first comprehensive analysis of membrane phospholipids and glycolipids in the important human pathogen E. faecalis, for which antimicrobial resistance and altered lipid homeostasis have been intimately linked.


Subject(s)
Anti-Bacterial Agents/pharmacology , Daptomycin/pharmacology , Drug Resistance, Multiple, Bacterial/drug effects , Enterococcus faecalis/drug effects , Lysine/metabolism , Phosphatidylglycerols/metabolism , Biotransformation , Cardiolipins/classification , Cardiolipins/isolation & purification , Cardiolipins/metabolism , Chromatography, Liquid , Diglycerides/classification , Diglycerides/isolation & purification , Diglycerides/metabolism , Drug Resistance, Multiple, Bacterial/physiology , Enterococcus faecalis/growth & development , Enterococcus faecalis/metabolism , Lipid Metabolism , Lysine/classification , Lysine/isolation & purification , Metabolomics , Phosphatidylglycerols/classification , Phosphatidylglycerols/isolation & purification , Tandem Mass Spectrometry , Triglycerides/classification , Triglycerides/isolation & purification , Triglycerides/metabolism
6.
Free Radic Biol Med ; 53(9): 1697-707, 2012 Nov 01.
Article in English | MEDLINE | ID: mdl-22940494

ABSTRACT

This article demonstrates a role for intracellular reactive oxygen species in the hyperphosphorylation of Akt in cells that have lost the expression of the tumor suppressor PTEN. Using mouse embryonic fibroblasts in which the expression of PTEN was knocked out, we show that a decrease in intracellular superoxide anion resulted in a rapid dephosphorylation of Akt at Thr308 followed by Ser473. Whereas dephosphorylation was detected in the cytosolic pool of Akt, phosphorylation of the membrane pool of the kinase remained unaffected. Dephosphorylation of cytosolic Akt was attributed to an increase in the interaction between Akt and the catalytic subunit of the protein phosphatase PP2A, which correlated with an increase in the amount of the oxidized versus the reduced form of the kinase. These results were corroborated in the PTEN knockout prostate cancer cell line LNCaP and in the melanoma cell line M14 stably transfected with a constitutively active form of Rac1.


Subject(s)
Cytoplasm/enzymology , PTEN Phosphohydrolase/deficiency , Protein Processing, Post-Translational , Proto-Oncogene Proteins c-akt/metabolism , Animals , Cell Line , Fibroblasts/drug effects , Fibroblasts/enzymology , Fibroblasts/metabolism , Glycogen Synthase Kinase 3/metabolism , Humans , Mice , Mice, Knockout , NADH, NADPH Oxidoreductases/antagonists & inhibitors , NADPH Oxidase 1 , NADPH Oxidase 4 , NADPH Oxidases/metabolism , Onium Compounds/pharmacology , Oxidation-Reduction , Phosphorylation , Protein Binding , Protein Phosphatase 2/antagonists & inhibitors , Protein Phosphatase 2/metabolism , Superoxides/metabolism
7.
J Cell Biol ; 192(1): 121-35, 2011 Jan 10.
Article in English | MEDLINE | ID: mdl-21220512

ABSTRACT

Oxysterol-binding protein (OSBP) and its related proteins (ORPs) constitute a large and evolutionarily conserved family of lipid-binding proteins that target organelle membranes to mediate sterol signaling and/or transport. Here we characterize ORP5, a tail-anchored ORP protein that localizes to the endoplasmic reticulum. Knocking down ORP5 causes cholesterol accumulation in late endosomes and lysosomes, which is reminiscent of the cholesterol trafficking defect in Niemann Pick C (NPC) fibroblasts. Cholesterol appears to accumulate in the limiting membranes of endosomal compartments in ORP5-depleted cells, whereas depletion of NPC1 or both ORP5 and NPC1 results in luminal accumulation of cholesterol. Moreover, trans-Golgi resident proteins mislocalize to endosomal compartments upon ORP5 depletion, which depends on a functional NPC1. Our results establish the first link between NPC1 and a cytoplasmic sterol carrier, and suggest that ORP5 may cooperate with NPC1 to mediate the exit of cholesterol from endosomes/lysosomes.


Subject(s)
Cholesterol/metabolism , Endosomes/metabolism , Receptors, Steroid/metabolism , Biological Transport , Carrier Proteins/metabolism , Endoplasmic Reticulum/metabolism , Esterification , Gene Knockdown Techniques , Golgi Apparatus/metabolism , HeLa Cells , Humans , Immunoprecipitation , Intracellular Membranes/metabolism , Intracellular Signaling Peptides and Proteins , Lipoproteins, LDL/metabolism , Lysosomes/metabolism , Membrane Glycoproteins/metabolism , Niemann-Pick C1 Protein , Protein Binding , Protein Structure, Tertiary , RNA, Small Interfering/metabolism , Receptors, Steroid/chemistry , Saccharomyces cerevisiae Proteins/metabolism , Shiga Toxin/metabolism
8.
Int J Biochem Cell Biol ; 43(4): 594-603, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21187157

ABSTRACT

The present report investigated the pathway(s) involved in the inhibition of apoptosis by the synthetic androgen, R1881 in serum-starved LNCaP cells exposed to the pi3K inhibitor, LY294002. R1881 blocked LY294002-induced apoptosis through the inhibition of Bak activation via an increase in Bcl-xL transcription and protein expression. In addition, R1881 treatment enhanced the stability of the Pim-1 kinase, resulting in the inhibition of the activation of the BH3-only protein Bad through its phosphorylation at ser75. Pharmacological inhibition of the Pim-1 kinase activity with quercetagetin, a highly selective Pim-1 inhibitor, prevented R1881-mediated increase in Bad phosphorylation and restored cell sensitivity to LY294002-induced apoptosis despite the increase in Bcl-xL expression. These results demonstrate for the first time that the inhibition of LY294002-induced apoptosis by androgen is a function of an androgen receptor-dependent genomic signaling pathway leading to an increase in Bcl-xL expression as well as a non-genomic, Pim-1-dependent, signaling pathway mediated via phosphorylation of Bad at ser75.


Subject(s)
Androgens/pharmacology , Metribolone/pharmacology , Proto-Oncogene Proteins c-pim-1/metabolism , Serine/metabolism , bcl-Associated Death Protein/chemistry , bcl-Associated Death Protein/metabolism , bcl-X Protein/metabolism , Cell Line, Tumor , Cell Survival/drug effects , Chromones/antagonists & inhibitors , Chromones/pharmacology , Culture Media, Serum-Free , Enzyme Activation/drug effects , Enzyme Stability/drug effects , Gene Expression Regulation/drug effects , Half-Life , Humans , Morpholines/antagonists & inhibitors , Morpholines/pharmacology , Phosphorylation/drug effects , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Proto-Oncogene Proteins c-pim-1/chemistry , Signal Transduction/drug effects , bcl-2 Homologous Antagonist-Killer Protein/antagonists & inhibitors , bcl-2 Homologous Antagonist-Killer Protein/metabolism , bcl-X Protein/genetics
9.
Appl Microbiol Biotechnol ; 80(4): 555-61, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18607587

ABSTRACT

Lysostaphin is a zinc metalloenzyme which has a specific lytic action against Staphylococcus aureus. Lysostaphin has activities of three enzymes namely, glycylglycine endopeptidase, endo-beta-N-acetyl glucosamidase and N-acteyl muramyl-L-alanine amidase. Glycylglycine endopeptidase specifically cleaves the glycine-glycine bonds, unique to the interpeptide cross-bridge of the S. aureus cell wall. Due to its unique specificity, lysostaphin could have high potential in the treatment of antibiotic-resistant staphylococcal infections. This review article presents a current understanding of the lysostaphin and its applications in therapeutic agent as a treatment against antibiotic-resistant S. aureus and methicillin-resistant S. aureus (MRSA) infections, either alone or in combination with other antibiotics.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Lysostaphin/therapeutic use , Staphylococcal Infections/drug therapy , Staphylococcus aureus/drug effects , Animals , Anti-Bacterial Agents/immunology , Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial , Drug Stability , Humans , Lysostaphin/immunology , Lysostaphin/pharmacology , Pharmaceutical Preparations , Staphylococcal Infections/immunology
10.
Proc Natl Acad Sci U S A ; 101(26): 9562-7, 2004 Jun 29.
Article in English | MEDLINE | ID: mdl-15205484

ABSTRACT

Repair of double-strand breaks is essential for the maintenance of genome integrity and cell survival. In eukaryotes, double-strand-break repair by homologous recombination requires the Rad52 group of proteins. Human Rad52 protein (HsRad52)-mediated annealing of complementary strands has been studied in detail, but little has been reported on the recombinase activities of HsRad52. For this study, we purified HsRad52 from Escherichia coli. DNase I protection experiments indicated that HsRad52 binds preferentially to single-stranded DNA and protects it against digestion by DNase I. HsRad52 catalyzed D-loop formation in superhelical DNA, as well as strand exchange among oligonucleotide substrates. The formation of a stoichiometric complex between HsRad52 and single-stranded DNA was found to be critical for strand exchange activity, and the coating of both the single- and double-stranded oligonucleotides inhibited the exchange reaction.


Subject(s)
DNA, Single-Stranded/metabolism , DNA-Binding Proteins/metabolism , Recombination, Genetic , Binding Sites , Catalysis , Chromosome Pairing , DNA, Single-Stranded/chemistry , DNA, Single-Stranded/genetics , Deoxyribonuclease I/metabolism , Escherichia coli , Humans , Nuclease Protection Assays , Nucleic Acid Conformation , Oligodeoxyribonucleotides/chemistry , Oligodeoxyribonucleotides/genetics , Oligodeoxyribonucleotides/metabolism , Protein Binding , Rad51 Recombinase , Rad52 DNA Repair and Recombination Protein , Rec A Recombinases/metabolism , Recombinant Proteins/metabolism
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