Thioredoxin 80-Activated-Monocytes (TAMs) Inhibit the Replication of Intracellular Pathogens

BACKGROUND: Thioredoxin 80 (Trx80) is an 80 amino acid natural cleavage product of Trx, produced primarily by monocytes. Trx80 induces differentiation of human monocytes into a novel cell type, named Trx80-activated-monocytes (TAMs). PRINCIPAL FINDINGS: In this investigation we present evidence for a role of TAMs in the control of intracellular bacterial infections. As model pathogens we have chosen Listeria monocytogenes and Brucella abortus which replicate in the cytosol and the endoplasmic reticulum respectively. Our data indicate that TAMs efficiently inhibit intracellular growth of both L. monocytogenes and B. abortus. Further analysis shows that Trx80 activation prevents the escape of GFP-tagged L. monocytogenes into the cytosol, and induces accumulation of the bacteria within the lysosomes. Inhibition of the lysosomal activity by chloroquine treatment resulted in higher replication of bacteria in TAMs compared to that observed in control cells 24 h post-infection, indicating that TAMs kill bacteria by preventing their escape from the endosomal compartments, which progress into a highly degradative phagolysosome. SIGNIFICANCE: Our results show that Trx80 potentiates the bactericidal activities of professional phagocytes, and contributes to the first line of defense against intracellular bacteria

Phenotype-dependent apoptosis signalling in mesothelioma cells after selenite exposure

<p>Abstract</p> <p>Background</p> <p>Selenite is a promising anticancer agent which has been shown to induce apoptosis in malignant mesothelioma cells in a phenotype-dependent manner, where cells of the chemoresistant sarcomatoid phenotype are more sensitive.</p> <p>Methods</p> <p>In this paper, we investigate the apoptosis signalling mechanisms in sarcomatoid and epithelioid mesothelioma cells after selenite treatment. Apoptosis was measured with the Annexin-PI assay. The mitochondrial membrane potential, the expression of Bax, Bcl-XL, and the activation of caspase-3 were assayed with flow cytometry and a cytokeratin 18 cleavage assay. Signalling through JNK, p38, p53, and cathepsins B, D, and E was investigated with chemical inhibitors. Furthermore, the expression, nuclear translocation and DNA-binding activity of p53 was investigated using ICC, EMSA and the monitoring of p21 expression as a downstream event. Levels of thioredoxin (Trx) were measured by ELISA.</p> <p>Results</p> <p>In both cell lines, 10 μM selenite caused apoptosis and a marked loss of mitochondrial membrane potential. Bax was up-regulated only in the sarcomatoid cell line, while the epithelioid cell line down-regulated Bcl-XL and showed greater caspase-3 activation. Nuclear translocation of p53 was seen in both cell lines, but very little p21 expression was induced. Chemical inhibition of p53 did not protect the cells from apoptosis. p53 lost its DNA binding ability after selenite treatment and was enriched in an inactive form. Levels of thioredoxin decreased after selenite treatment. Chemical inhibition of MAP kinases and cathepsins showed that p38 and cathepsin B had some mediatory effect while JNK had an anti-apoptotic role.</p> <p>Conclusion</p> <p>We delineate pathways of apoptosis signalling in response to selenite, showing differences between epithelioid and sarcomatoid mesothelioma cells. These differences may partly explain why sarcomatoid cells are more sensitive to selenite.</p

Transcriptome Analysis Describing New Immunity and Defense Genes in Peripheral Blood Mononuclear Cells of Rheumatoid Arthritis Patients

Background: Large-scale gene expression profiling of peripheral blood mononuclear cells from Rheumatoid Arthritis (RA) patients could provide a molecular description that reflects the contribution of diverse cellular responses associated with this disease. The aim of our study was to identify peripheral blood gene expression profiles for RA patients, using Illumina technology, to gain insights into RA molecular mechanisms. Methodology/Principal Findings: The Illumina Human-6v2 Expression BeadChips were used for a complete genome-wide transcript profiling of peripheral blood mononuclear cells (PBMCs) from 18 RA patients and 15 controls. Differential analysis per gene was performed with one-way analysis of variance (ANOVA) and P values were adjusted to control the False Discovery Rate (FDR < 5%). Genes differentially expressed at significant level between patients and controls were analyzed using Gene Ontology (GO) in the PANTHER database to identify biological processes. A differentially expression of 339 Reference Sequence genes (238 down-regulated and 101 up-regulated) between the two groups was observed. We identified a remarkably elevated expression of a spectrum of genes involved in Immunity and Defense in PBMCs of RA patients compared to controls. This result is confirmed by GO analysis, suggesting that these genes could be activated systemically in RA. No significant down-regulated ontology groups were found. Microarray data were validated by real time PCR in a set of nine genes showing a high degree of correlation. Conclusions/Significance: Our study highlighted several new genes that could contribute in the identification of innovative clinical biomarkers for diagnostic procedures and therapeutic interventions

Comparison of four surgical approaches for rectal prolapse : multicentre randomized clinical trial

Background: Several different procedures have been described for surgical treatment of rectal prolapse and consensus on the optimal approach has not been reached. The Swedish Rectal Prolapse Trial was performed with the aim to compare the outcomes after the most common surgical approaches to rectal prolapse. Method: A multicentre randomized trial was conducted from 2000 to 2009. Patients were randomized between a perineal or an abdominal approach for correction of rectal prolapse (randomization A) if eligible for any procedures. Patients considered unsuitable for random allocation were only included in randomizations B or C. Patients in randomization B (perineal group) were randomized to Delorme's or Altemeier's procedures and those in randomization C (abdominal group) to suture rectopexy or resection rectopexy. Primary outcomes were bowel function and quality of life, measured using Wexner incontinence score and RAND-36, and secondary outcomes were complications and recurrence at 3 years. Results: During the study period, 134 patients were randomized: 18 in randomization A group, 80 in randomization B group and 54 in randomization C group; of these, 122 patients underwent surgery. Mean follow-up was 2.6 years. Improvements in Wexner and RAND36 scores were seen but with no significant difference between the groups. Health change scores were significantly improved from baseline up to 1 year after surgery (P &lt; 0.001). At 3 years, recurrence rates were two of seven patients for abdominal versus five of eight patients for perineal approach (P = 0.315), 18 of 31 patients (58 per cent) for Delorme's versus 15 of 30 patients (50 per cent) for Altemeier's (P = 0.611) and four of 19 patients (21 per cent) for suture rectopexy versus two of 21 patients (10 per cent) for resection rectopexy (P = 0.398). There were no significant differences regarding postoperative complications. Conclusion: For all procedures, significant improvements from baseline in health change scores were noted after surgery. Recurrence rates were higher than previously reported

Patient safety with orthognathic surgery in an outpatient setting

Orthognathic surgery is traditionally performed in inpatient care. The question is whether patient safety is maintained when orthognathic surgery is performed in outpatient care. This retrospective cohort study was conducted to investigate patient safety in selected single-jaw orthognathic surgeries performed in outpatient care compared to inpatient care. Postoperative infection, postoperative bleeding, postoperative pain, plate removal, and re-operation, as well as emergency visits/phone calls and postoperative admission during the first 12 months after surgery were recorded. Predictor variables were sex, age, smoking, general disease, antibiotics, operation type, and operation time. Of the 165 patients included, 58 were treated in inpatient care and 107 in outpatient care. No significant difference was found between the groups regarding postoperative bleeding, pain, plate removal, re-operation, or emergency visits/phone calls. Ninety-four percent of outpatients (n = 101) were able to leave the hospital on the day of surgery as planned. There was an increased risk of postoperative infection in the outpatient care group (odds ratio 2.46, P = 0.049). Selected single-jaw orthognathic surgery can be performed in the outpatient setting, with maintained patient safety. The reason for the increased risk of postoperative infection among patients operated in outpatient care should be investigated in further studies

Guided selective deposition of nanoparticles by tuning of the surface potential

Guided deposition of nanoparticles onto different substrates is of great importance for a variety of applications such as biosensing, targeted cancer therapy, anti-bacterial coatings and single molecular electronics. It is therefore important to gain an understanding of what parameters are involved in the deposition of nanoparticles. In this work we have deposited 60 nm, negatively charged, citrate stabilized gold nanoparticles onto microstructures consisting of six different materials, (vanadium (V), silicon dioxide (SiO2), gold (Au), aluminum (Al), copper (Cu) and nickel (Ni)). The samples have then been investigated by scanning electron microscopy to extract the particle density. The surface potential was calculated from the measured surface charge density maps measured by atomic force microscopy while the samples were submerged in a KCl water solution. These values were compared with literature values of the isoelectric points (IEP) of different oxides formed on the metals in an ambient environment. According to measurements, Al had the highest surface potential followed by Ni and Cu. The same trend was observed for the nanoparticle densities. No particles were found on V, SiO2 and Au. The literature values of the IEP showed a different trend compared to the surface potential measurements concluding that IEP is not a reliable parameter for the prediction of NP deposition. focus article Copyright (C) EPLA, 201