Effect of a Non-Newtonian Load on Signature S

The quartz crystal microbalance (QCM) is increasingly used for monitoring the interfacial interaction between surfaces and macromolecules such as biomaterials, polymers, and metals. Recent QCM applications deal with several types of liquids with various viscous macromolecule compounds, which behave differently from Newtonian liquids. To properly monitor such interactions, it is crucial to understand the influence of the non-Newtonian fluid on the QCM measurement response. As a quantitative indicator of non-Newtonian behavior, we used the quartz resonator signature, S2, of the QCM measurement response, which has a consistent value for Newtonian fluids. We then modified De Kee’s non-Newtonian three-parameter model to apply it to our prediction of S2 values for non-Newtonian liquids. As a model, we chose polyethylene glycol (PEG400) with the titration of its volume concentration in deionized water. As the volume concentration of PEG400 increased, the S2 value decreased, confirming that the modified De Kee’s three-parameter model can predict the change in S2 value. Collectively, the findings presented herein enable the application of the quartz resonator signature, S2, to verify QCM measurement analysis in relation to a wide range of experimental subjects that may exhibit non-Newtonian behavior, including polymers and biomaterials

Quartz Crystal Microbalance as a Sensor to Characterize Macromolecular Assembly Dynamics

The quartz crystal microbalance sensor has a resonant frequency and a quality factor which can be used to probe the properties of nanometer thick film loads. A recent review by Arnau (2008) has discussed many of the considerations necessary to accurately probe for these properties. To avoid needless duplication but to still provide an adequate background for the new user, we briefly outline the basic measurement methodologies and analytical techniques that were covered in the review. Details will be provided on some specific perspectives of the authors. For example, the special precautions necessary when dealing with soft films (polymeric and biological) under liquid are overviewed. To illustrate applications of the QCM technique, simple bilayer and vesicle behaviors are discussed, along with the structural transformation resulting from protein adsorption onto an intact vesicle adlayer. The amphipathic -helical (AH) peptide interaction is given as a particular example. Lastly, we summarize a top-down approach to functionalize a surface with a cell membrane and to study its interaction with proteins

Method of fabricating lipid bilayer membranes on solid supports

The present invention provides a method of producing a planar lipid bilayer on a solid support. With this method, a solution of lipid vesicles is first deposited on the solid support. Next, the lipid vesicles are destabilized by adding an amphipathic peptide solution to the lipid vesicle solution. This destabilization leads to production of a planar lipid bilayer on the solid support. The present invention also provides a supported planar lipid bilayer, where the planar lipid bilayer is made of naturally occurring lipids and the solid support is made of unmodified gold or titanium oxide. Preferably, the supported planar lipid bilayer is continuous. The planar lipid bilayer may be made of any naturally occurring lipid or mixture of lipids, including, but not limited to phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinsitol, cardiolipin, cholesterol, and sphingomyelin

Amphipathic Alpha-Helical Peptide Compositions as Antiviral Agents

The invention features methods and compositions that exploit the ability of amphipathic alpha-helical (AH) peptides to cause disruption of lipid-containing vesicles, such as enveloped viruses, in a size-dependent manner

An Electrophilic Deguelin Analogue Inhibits STAT3 Signaling in H-Ras-Transformed Human Mammary Epithelial Cells: The Cysteine 259 Residue as a Potential Target

Signal transducer and activator of transcription 3 (STAT3) is a point of convergence for numerous oncogenic signals that are often constitutively activated in many cancerous or transformed cells and some stromal cells in the tumor microenvironment. Persistent STAT3 activation in malignant cells stimulates proliferation, survival, angiogenesis, invasion, and tumor-promoting inflammation. STAT3 undergoes activation through phosphorylation on tyrosine 705, which facilitates its dimerization. Dimeric STAT3 translocates to the nucleus, where it regulates the transcription of genes involved in cell proliferation, survival, etc. In the present study, a synthetic deguelin analogue SH48, discovered by virtual screening, inhibited the phosphorylation, nuclear translocation, and transcriptional activity of STAT3 in H-ras transformed human mammary epithelial MCF-10A cells (MCF10A-ras). We speculated that SH48 bearing an alpha,beta-unsaturated carbonyl group could interact with a thiol residue of STAT3, thereby inactivating this transcription factor. Non-electrophilic analogues of SH48 failed to inhibit STAT3 activation, lending support to the above supposition. By utilizing a biotinylated SH48, we were able to demonstrate the complex formation between SH48 and STAT3. SH48 treatment to MCF10A-ras cells induced autophagy, which was verified by staining with a fluorescent acidotropic probe, LysoTracker Red, as well as upregulating the expression of LC3II and p62. In conclusion, the electrophilic analogue of deguelin interacts with STAT3 and inhibits its activation in MCF10A-ras cells, which may account for its induction of autophagic death.

Single-Session Percutaneous Mechanical Thrombectomy for Acute and Subacute Deep Vein Thrombosis: Clinical Outcomes and Predictive Factors of Recurrence

Objectives: To evaluate the efficacy and safety of single-session percutaneous mechanical thrombectomy (PMT) for deep vein thrombosis (DVT), to compare clinical outcomes and recurrences between acute and subacute DVT, and to identify factors predicting recurrence. Materials and Methods: From January 2018 to March 2021, 100 consecutive patients (age: 64.64 ± 17.28 years; male, 42%) with symptomatic DVT who underwent single-session PMT were enrolled for this study. These patients were divided into an acute DVT group (< 14 days, n = 75) and a subacute DVT group (15–28 days, n = 25). Results: A large-bore aspiration thrombectomy was used in 80 (80%) cases, Angiojet (Boston Scientific, Marlborough, MA, USA) device in one (1%) case, and a combination of both techniques in 19 (19%) cases. The anatomic success rate was 97% and the clinical success rate was 95%. There were no major complications. Clinical outcomes were not different between the two groups. The recurrence-free survival rate in the acute DVT group was significantly (p = 0.015) better than that in the subacute DVT group. The anatomic success (HR, 52.3; 95% CI, 3.82–715.21; p = 0.003) and symptom duration (HR, 17.58; 95% CI, 1.89–163.34; p = 0.012) were predictive factors associated with recurrence. Conclusions: Single-session PMT is safe and effective for immediate symptom relief in acute and subacute DVT patients. However, recurrence occurred more frequently in patients with subacute DVT than in those with acute DVT. Anatomic success of the procedure and duration of symptoms were independent predictors of DVT recurrence

Curcumin induces stabilization of Nrf2 protein through Keap1 cysteine modification

The present study was aimed to investigate the effects of curcumin, a representative chemopreventive phytochemical with pronounced antioxidant and anti-inflammatory properties, on activation of Nrf2 and expression of its target protein heme oxygenase-1 (HO-1) in mouse skin in vivo and in cultured murine epidermal cells. Treatment of mouse epidermal JB6 cells with curcumin resulted in the induction of HO-1 expression, and this was abrogated in cells transiently transfected with Nrf2 siRNA. While curcumin treatment increased protein expression of Nrf2, it did not alter the steady-state level of the Nrf2 mRNA transcript. Treatment of cells with curcumin stabilized Nrf2 by inhibiting ubiquitination and subsequent 26S proteasomal degradation of this transcription factor. Tetrahydrocurcumin, a non-electrophilic analogue of curcumin that lacks the alpha,beta-unsaturated carbonyl group, failed to induce HO-1 expression as well as nuclear translocation of Nrf2 and its binding to the antioxidant/electrophile response elements. Cells transfected with a mutant Keap1 protein in which cysteine 151 (Cys151) is replaced by serine exhibited marked reduction in curcumin-induced Nrf2 transactivation. Mass spectrometric analysis revealed that curcumin binds to Keap1 Cys151, supporting that this amino acid is a critical target for curcumin modification of Keap1, which facilitates the liberation of Nrf2. Thus, it is likely that the alpha,beta-unsaturated carbonyl moiety of curcumin is essential for its binding to Keap1 and stabilization of Nrf2 by hampering ubiquitination and proteasomal degradation.

High-Grade Hydronephrosis Predicts Poor Outcomes After Radical Cystectomy in Patients with Bladder Cancer

We examined whether the presence and severity of preoperative hydronephrosis have prognostic significance in patients who underwent radical cystectomy for transitional cell carcinoma of the bladder. The medical records of 457 patients who underwent radical cystectomy for bladder cancer between 1986 and 2005 were retrospectively reviewed. Following the Society for Fetal Urology grading system, patients were divided into low-, and high-grade hydronephrosis groups. Clinicopathologic factors associated with preoperative hydronephrosis and survival were evaluated. Of a total of 406 patients, unilateral hydronephrosis was found in 74 (18.2%), bilateral hydronephrosis in 11 (2.7%), and no hydronephoris in 321 (79.1%). Low-grade hydronephrosis was found in 57 (12.2%) patients and high-grade hydronephrosis in 28 (6%). Preoperative hydronephrosis was related to higher pT stage and lymph node invasion. In univariate analysis, the presence of hydronephrosis, hydronephrosis grade, age, pT and pN stage, tumor grade, surgical margin, number of retrieved nodes, carcinoma in situ, and lymphovascular invasion were significant prognostic factors for cancer-specific survival. In multivariate analysis, bilateral hydronephrosis and high-grade hydronephrosis remained significant predictors for decreased survival. The presence of preoperative hydronephrosis, and high-grade hydronephrosis are significant prognostic factors in patients with bladder cancer after radical cystectomy

17-Oxo-docosahexaenoic acid induces Nrf2-mediated expression of heme oxygenase-1 in mouse skin in vivo and in cultured murine epidermal cells

Recently, growing attention has been given to new classes of bioactive lipid mediators derived from omega-3 polyunsaturated fatty acids, such as docosahexaenoic acid (DHA), especially in the context of their role as endogenous signal modulators. One such molecule is 17-oxo-DHA, generated from DHA by the action of COX2 and a dehydrogenase. The redox-sensitive transcription factor, Nrf2 plays a key role in cellular stress responses. In the present study, the effects of 17-oxo-DHA on Nrf2-mediated expression of cytoprotective enzymes were examined in mouse skin in vivo and cultured murine epidermal JB6 cells. Topical application of 17-oxo-DHA markedly elevated the nuclear localization of Nrf2 and expression of heme oxygenase-1 (HO-1) and NAD(P) H:quinone oxidoreductase-1 in hairless mouse skin. In contrast to 17-oxo-DHA, the non-electrophilic metabolic precursor 17-hydroxy-DHA was a much weaker inducer of Nrf2 activation and its target protein expression. Likewise, 17-oxo-DHA significantly enhanced nuclear translocation and transcriptional activity of Nrf2 with concomitant upregulation of HO-1 expression in cultured JB6 cells. 17-Oxo-DHA was a much stronger inducer of Nrf2-mediated antioxidant response than its parent molecule, DHA. HO-1 expression was abolished in Nrf2 knockdown JB6 cells or embryo fibroblasts from Nrf2 knock out mice. 17-Oxo-DHA also markedly reduced the level of Keap1 protein by inducing ubiquitination. Mutation of Cys151 and Cys273 in Keap1 abrogated 17-oxo-DHA-induced ubiquitination and proteasome-mediated degradation of Keap1 as well as HO-1 expression, suggesting that these cysteine residues are putative sites for 17-oxo-DHA binding. Further, Keap1 degradation stimulated by 17-oxo-DHA coincided with accumulation of the autophagy substrate, p62/SQSTM1.

Imaging Findings of Castleman's Disease Localized in the Axilla: A Case Report

Castleman's disease is a rare benign lymphoproliferative disorder of uncertain origin which most commonly involves the mediastinum but rarely affects the axilla. We report a case of localized Castleman's disease involving the axillary lymph node. Mammography revealed a well-defined, homogeneously dense ovoid mass, 3 cm in size, in the left axilla, while gray-scale ultrasonography (US) demonstrated a well-defined, uniformly hypoechoic ovoid mass with good through transmission. Peripheral hypervascularity was observed at power Dopper US, and early rapid homogeneous enhancement at contrast-enhanced dynamic CT