Prostate cancer survivors with symptoms of radiation cystitis have elevated fibrotic and vascular proteins in urine

als.fakia shared this article with you from Inoreader Prostate cancer survivors with symptoms of radiation cystitis have elevated fibrotic and vascular proteins in urine Via PLOS ONE Alerts: New Articles by Bernadette M. M. Zwaans, Heinz E. Nicolai, Michael B. Chancellor, Laura E. Lamb Radiation for pelvic cancers can result in severe bladder damage and radiation cystitis (RC), which is characterized by chronic inflammation, fibrosis, and vascular damage. RC development is poorly understood because bladder biopsies are difficult to obtain. The goal of this study is to gain understanding of molecular changes that drive radiation-induced cystitis in cancer survivors using urine samples from prostate cancer survivors with history of radiation therapy. 94 urine samples were collected from prostate cancer survivors with (n = 85) and without (n = 9) history of radiation therapy. 15 patients with radiation history were officially diagnosed with radiation cystitis. Levels of 47 different proteins were measured using Multiplex Luminex. Comparisons were made between non-irradiated and irradiated samples, and within irradiated samples based on radiation cystitis diagnosis, symptom scores or hematuria. Statistical analysis was performed using Welch's t-test. In prostate canc er survivors with history of radiation therapy, elevated levels of PAI 1, TIMP1, TIMP2, HGF and VEGF-A were detected in patients that received a radiation cystitis diagnosis. These proteins were also increased in patients suffering from hematuria or high symptom scores. No inflammatory proteins were detected in the urine, except in patients with gross hematuria and end stage radiation cystitis. Active fibrosis and vascular distress is detectable in the urine through elevated levels of associated proteins. Inflammation is only detected in urine of patients with end-stage radiation cystitis disease. These results suggest that fibrosis and vascular damage drive the development of radiation cystitis and could lead to the development of more targeted treatments. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Mesenchymal stem cells promote metastasis through activation of an ABL-MMP9 signaling axis in lung cancer cells

als.fakia shared this article with you from Inoreader Mesenchymal stem cells promote metastasis through activation of an ABL-MMP9 signaling axis in lung cancer cells Via PLOS ONE Alerts: New Articles by Jing Jin Gu, Jacob Hoj, Clay Rouse, Ann Marie Pendergast Mesenchymal stem cells (MSCs) are recruited and activated by solid tumors and play a role in tumor progression and metastasis. Here we show that MSCs promote metastasis in a panel of non-small cell lung cancer (NSCLC) cells. MSCs elicit transcriptional alterations in lung cancer cells leading to increased expression of factors implicated in the epithelial-to-mesenchymal transition (EMT) and secreted proteins including matrix metalloproteinase-9 (MMP9). MSCs enhance secretion of enzymatically active MMP9 in a panel of lung adenocarcinoma cells. High expression of MMP9 is linked to low survival rates in lung adenocarcinoma patients. Notably, we found that ABL tyrosine kinases are activated in MSC-primed lung cancer cells and functional ABL kinases are required for MSC-induced MMP9 expression, secretion and proteolytic activity. Importantly, ABL kinases are required for MSC-induced NSCLC metastasis. These data reveal an actionable target for inhibiting MSC-induced metastatic acti vity of lung adenocarcinoma cells through disruption of an ABL kinase-MMP9 signaling axis activated in MSC-primed lung cancer cells. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Comparative proteomic analysis of silica-induced pulmonary fibrosis

als.fakia shared this article with you from Inoreader Comparative proteomic analysis of silica-induced pulmonary fibrosis in rats based on tandem mass tag (TMT) quantitation technology Via PLOS ONE Alerts: New Articles by Cunxiang Bo, Xiao Geng, Juan Zhang, Linlin Sai, Yu Zhang, Gongchang Yu, Zhenling Zhang, Kai Liu, Zhongjun Du, Cheng Peng, Qiang Jia, Hua Shao Silicosis is a systemic disease characterized by chronic persistent inflammation and incurable pulmonary fibrosis with the underlying molecular mechanisms to be fully elucidated. In this study, we employed tandem mass tag (TMT) based on quantitative proteomics technology to detect differentially expressed proteins (DEPs) in lung tissues of silica-exposed rats. A total of 285 DEPs (145 upregulated and 140 downregulated) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the biological pathway and functional classification of the proteins. Results showed that these DEPs were mainly enriched in the phagosome, lysosome function, complement and the coagulation cascade, glutathione metabolism, focal adhesion and ECM-receptor interactions. To validate the proteomics data, we selected and analyzed the expression trends of six proteins including CD14, PSAP, GM2A, COL1A1, ITGA8 and CLDN5 using parallel reaction monitoring ( PRM). The consistent result between PRM and TMT indicated the reliability of our proteomic data. These findings will help to reveal the pathogenesis of silicosis and provide potential therapeutic targets. Data are available via ProteomeXchange with identifier PXD020625. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Extent of arterial calcification by conventional vitamin K antagonist treatment

als.fakia shared this article with you from Inoreader Extent of arterial calcification by conventional vitamin K antagonist treatment Via PLOS ONE Alerts: New Articles by Selma Hasific, Kristian Altern Øvrehus, Oke Gerke, Jesper Hallas, Martin Busk, Jess Lambrechtsen, Grazina Urbonaviciene, Niels Peter Rønnow Sand, Jens Steen Nielsen, Louise Diederichsen, Kenneth Bruun Pedersen, Rasmus Carter-Storch, Nivethitha Ilangkovan, Hans Mickley, Lars Melholt Rasmussen, Jes Sandal Lindholt, Axel Diederichsen Background and aims Vitamin K antagonists (VKA) remain the most frequently prescribed oral anticoagulants worldwide despite the introduction of non-vitamin K antagonist oral anticoagulants (NOAC). VKA interfere with the regeneration of Vitamin K1 and K2, essential to the activation of coagulation factors and activation of matrix-Gla protein, a strong inhibitor of arterial calcifications. This study aimed to clarify whether VKA treatment was associated with the extent of coronary artery calcification (CAC) in a population with no prior cardiovascular disease (CVD). Methods We collected data on cardiovascular risk factors and CAC scores from cardiac CT scans performed as part of clinical examinations (n = 9,672) or research studies (n = 14,166) in the period 2007–2017. Data on use of anticoagulation were obtained from the Danish National Health Service Prescription Database. The association between duration of anticoagulation and categorized CAC score (0, 1–99, 100–399, ≥400) was investigated by ordered logistic regression adjusting for covariates. Results The final study population consisted of 17,254 participants with no prior CVD, of whom 1,748 and 1,144 had been treated with VKA or NOAC, respectively. A longer duration of VKA treatment was associated with higher CAC categories. For each year of VKA treatment, the odds of being in a higher CAC category increased (odds ratio (OR) = 1.032, 95%CI 1.009–1.057). In contrast, NOAC treatment duration was not associated with CAC category (OR = 1.002, 95%CI 0.935–1.074). There was no significant interaction between VKA treatment duration and age on CAC category. Conclusions Adjusted for cardiovascular risk factors, VKA treatment–contrary to NOAC—was associated to higher CAC category. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Synergistic effect of collagen and CXCL12 in the low doses on human platelet activation

als.fakia shared this article with you from Inoreader Synergistic effect of collagen and CXCL12 in the low doses on human platelet activation Via PLOS ONE Alerts: New Articles by Daiki Nakashima, Takashi Onuma, Kumiko Tanabe, Yuko Kito, Kodai Uematsu, Daisuke Mizutani, Yukiko Enomoto, Masanori Tsujimoto, Tomoaki Doi, Rie Matsushima-Nishiwaki, Haruhiko Tokuda, Shinji Ogura, Toru Iwama, Osamu Kozawa, Hiroki Iida CXCL12, also known as stromal cell-derived factor-1, is a chemokine classified into CXC families, which exerts its function by binding to specific receptors called CXCR4 and CXCR7. Human platelets express CXCR4 and CXCR7 on the plasma membrane. It has been reported that CXCL12 potentiates to induce platelet aggregation in cooperation with agonists including collagen. However, the precise roles and mechanisms of CXCL12 in human platelet activation are not fully elucidated. In the present study, we investigated the effect of simultaneous stimulation with low doses of collagen and CXCL12 on the activation of human platelets. The simultaneous stimulation with collagen and CXCL12 induced the secretion of platelet-derived growth factor (PDGF)-AB and the release of soluble CD40 ligand (sCD40L) from human platelets in addition to their aggregation, despite the fact that the simultaneous stimulation with thrombin receptor-activating peptide (TRAP) or adenosine diphosphate (ADP), and CXCL12 ha d little effects on the platelet aggregation. The agonist of Glycoprotein (GP) Ⅵ convulxin and CXCL12 also induced platelet aggregation synergistically. The monoclonal antibody against CXCR4 but not CXCR7 suppressed the platelet aggregation induced by simultaneous stimulation with collagen and CXCL12. The phosphorylation of p38 mitogen-activated protein kinase (MAPK), but not p44/p42 MAPK, was induced by the simultaneous stimulation. In addition, the simultaneous stimulation with collagen and CXCL12 induced the phosphorylation of HSP27 and the subsequent release of phosphorylated-HSP27 from human platelets. SB203580, a specific inhibitor of p38 MAPK, attenuated the platelet aggregation, the phosphorylation of p38 MAPK and HSP27, the PDGF-AB secretion, the sCD40L release and the phosphorylated-HSP27 release induced by the simultaneous stimulation with collagen and CXCL12. These results strongly suggest that collagen and CXCL12 in low doses synergistically act to induce PDGF-AB secr etion, sCD40L release and phosphorylated-HSP27 release from activated human platelets via p38 MAPK activation. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Facilitators and barriers to engagement with contact tracing during infectious disease outbreaks: A rapid review of the evidence

als.fakia shared this article with you from Inoreader Facilitators and barriers to engagement with contact tracing during infectious disease outbreaks: A rapid review of the evidence Via PLOS ONE Alerts: New Articles by Odette Megnin-Viggars, Patrice Carter, G. J. Melendez-Torres, Dale Weston, G. James Rubin Background Until a vaccine is developed, a test, trace and isolate strategy is the most effective method of controlling the COVID-19 outbreak. Contact tracing and case isolation are common methods for controlling infectious disease outbreaks. However, the effectiveness of any contact tracing system rests on public engagement. Numerous factors may influence an individual's willingness to engage with a contact tracing system. Understanding these factors has become urgent during the COVID-19 pandemic. Objective To identify facilitators and barriers to uptake of, and engagement with, contact tracing during infectious disease outbreaks. Method A rapid systematic review was conducted to identify papers based on primary research, written in English, and that assessed facilitators, barriers, and other factors associated with the uptake of, and engagement with, a contact tracing system. Principal findings Four themes were identified as facilitators to the uptake of, and engagement with, contact tracing: collective responsibility; personal benefit; co-production of contact tracing systems; and the perception of the system as efficient, rigorous and reliable. Five themes were identified as barriers to the uptake of, and engagement with, contact tracing: privacy concerns; mistrust and/or apprehension; unmet need for more information and support; fear of stigmatization; and mode-specific challenges. Conclusions By focusing on the factors that have been identified, contact tracing services are more likely to get people to engage with them, identify more potentially ill contacts, and reduce transmission. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Six-minute stepper test in hospitalized elderly patients: Convergent validity, test-retest reliability and safety

als.fakia shared this article with you from Inoreader Six-minute stepper test in hospitalized elderly patients: Convergent validity, test-retest reliability and safety Via PLOS ONE Alerts: New Articles by Davi de Souza Francisco, Larissa Martinez, Aline Carleto Terrazas, Diego Britto Ribeiro, Wellington Pereira Yamaguti Objective To evaluate the convergent validity of the six-minute stepper test (6MST) with the variables used in the diagnosis of sarcopenia (appendicular muscle mass, handgrip strength and six-meter gait speed test), as well as to evaluate test-retest reliability and safety when applied to hospitalized elderly patients. Finally, we aimed to compare the performance in the 6MST between hospitalized elderly patients and healthy elderly from the community. Materials and methods Observational and cross-sectional study. Elderly patients admitted to a private hospital and healthy elderly from the community were recruited. On the first day, the patients included underwent the following assessments: anthropometric, handgrip strength (HGS), six-meter gait speed test (6GST) and 6MST. On the second day, before breakfast, patients underwent body composition assessment. The healthy elderly were evaluated on a single day and performed only anthropometric assessment and 6MST. Results 30 hospitalized patients (age 71.0±7.9 years) and 15 healthy elderly (age 68.1±5.8 years) were included. There was a high correlation of 6MST with 6GST (r = 0.78; p Conclusion 6MST showed convergent validity with the functional variables used in the diagnosis of sarcopenia. In addition, excellent test-retest reliability was observed, which indicates the need for a single assessment in hospitalized elderly patients. The prevalence of adverse events during the application of the test is low, without resulting in clinical symptoms; therefore, the test is considered safe for this population. In addition, hospitalized elderly patients perform worse in the 6MST compared to healthy elderly from the community. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.