Specific Ion Effects on Protein Thermal Aggregation from Dilute Solutions to Crowded Environments

We have investigated specific ion effects on protein thermal aggregation from dilute solutions to crowded environments. Ovalbumin and poly­(ethylene glycol) have been employed as the model protein and crowding agent, respectively. Our studies demonstrate that the rate-limiting step of ovalbumin thermal aggregation is changed from the aggregation of unfolded protein molecules to the unfolding of the protein molecules, when the solution conditions are varied from a dilute solution to a crowded environment. The specific ion effects acting on the thermal aggregation of ovalbumin generated by kosmotropic and chaotropic ions are different. The thermal aggregation of ovalbumin molecules is promoted by kosmotropic anions in dilute solutions via an increase in protein hydrophobic interactions. In contrast, ovalbumin thermal aggregation is facilitated by chaotropic ions in crowded environments through accelerated unfolding of protein molecules. Therefore, there are distinct mechanisms causing the ion specificities of protein thermal aggregation between dilute solutions and crowded environments. The ion specificities are dominated by ion-specific hydrophobic interactions between protein molecules and ion-specific unfolding of protein molecules in dilute solutions and crowded environments, respectively

Rate of bleeding-related episodes in elderly patients with primary immune thrombocytopenia: a retrospective cohort study

<p><b>Objective:</b> Immune thrombocytopenia (ITP) is characterized by low platelet counts and a tendency toward increased bleeding and bruising. We aimed to describe bleeding frequency and use of rescue ITP therapy to treat or prevent bleeding in elderly ITP patients in a real-world setting.</p> <p><b>Methods:</b> Using Medicare 20% sample data, 2007–2012, we identified elderly (ages ≥67 years) Medicare fee-for-service enrollees diagnosed with primary ITP between 1 January 2009 and 30 September 2012. Bleeding-related episodes (BREs) were defined as ≥1 bleeding event or use of ITP therapies commonly considered for rescue or emergency therapy. BRE rates were examined for the cohort overall, by time since ITP onset, and by splenectomy status. Patients were followed from ITP onset until the earliest of death, disenrollment from fee-for-service coverage, or 31 December 2012.</p> <p><b>Results:</b> We identified 3007 elderly patients diagnosed with primary ITP (mean [SD] age: 79.6 [7.5] years; 55% female); 2178 (72%) experienced at least one BRE (8867 BREs); 92 (3%) underwent splenectomy. Nearly half of BREs were defined by rescue therapy use alone. The overall rate was 1.72 BREs per patient-year (95% CI; 1.68–1.75); rates were higher during the first 3 months after ITP onset and after splenectomy.</p> <p><b>Conclusion:</b> Elderly ITP patients experienced about two BREs per patient-year after ITP onset. Most patients experienced at least one BRE. These real-world results demonstrate the importance of examining both bleeding and use of rescue or emergency ITP therapy in the assessment of disease burden in elderly patients with ITP.</p

miRNAs that are Dysregulated in cancer correlated with cancer differentiation.

<p>(A) Compared with normal tissues, a total of 93 miRNAs that were significantly dysregulated were identified, (B) 58 dysregulated miRNAs were found in moderately differentiated tissues compared with well-differentiated tissues, (C) 32 miRNAs were not only able to identify cancers samples and normal controls, but they were also able to distinguish between well- and moderately differentiated tumors.</p

miRNAs that are dysregulated in cancer tissues compared with normal controls by non-paired t-test that have rarely been mentioned in the literature.

<p>miRNAs that are dysregulated in cancer tissues compared with normal controls by non-paired t-test that have rarely been mentioned in the literature.</p

Evaluation of the potential of miR-4510, miR-99b and miR-4469 as cancer biomarkers.

<p>The results show that miR-4510, miR-99b and miR-4469 are highly likely to be diagnostic markers with high sensitivity and specificity.</p

miRNAs that were not only able to distinguish cancer patients from normal controls but also able to distinguish well-differentiated and moderately differentiated cancers.

<p>miRNAs that were not only able to distinguish cancer patients from normal controls but also able to distinguish well-differentiated and moderately differentiated cancers.</p

Clinical and histopathological characteristics of patients.

<p>Clinical and histopathological characteristics of patients.</p

Analysis of the expression levels of miR-1, miR-145*, miR-4510 and miR-4469 between well- and moderately differentiated tumors according to a non-paired t-test.

<p>The results show no obvious differences in the expression levels of miR-1, miR-145*, miR-4510 and miR-4469 between well- and moderately differentiated tumors (<i>P</i>>0.05).</p

Expression levels of miR-1, miR-145, miR-145*, miR-99b, miR-4510, and miR-4469 in an independent sample test.

<p>Expression levels of miR-1, miR-145, miR-145*, miR-99b, miR-4510, and miR-4469 in an independent sample test.</p

Dysregulated miRNAs in cancer tissues compared with normal controls by non-paired t-test.

<p>Dysregulated miRNAs in cancer tissues compared with normal controls by non-paired t-test.</p