Inner surface modification of ureteral stent polyurethane tubes based by plasma-enhanced chemical vapor deposition to reduce encrustation and biofilm formation.

Encrustation and/or biofilm formation in ureteral stents are major causes of obstruction and reduce the lifetime of a ureteral stent. In this study, the inner surfaces of polyurethane (PU) tubes (inner and outer diameters of 1.2 and 2.0 mm, respectively) were reformed with Ar, O2, and C2H2 gases using specialized plasma-enhanced chemical vapor deposition techniques for the first time. Then, the modified PU tubes were immersed in urine for 15 days, and the characteristics of the inner surfaces were analyzed. Depending on the modification procedure, the corresponding inner surface exhibited different chemical properties and different rates of encrustation and biofilm formation. For a hydrophilic surface treated with Ar and O2, encrustation and biofilm formation increased, while for the C2H2 coating, the development of encrustation and biofilm reduced by more than five times compared with the untreated bare PU tube. This study demonstrated that inner plasma surface modification of ureteral stents greatly enhances resistance to encrustation and biofilm formation.

Surface modification of polystyrene Petri dishes by plasma polymerized 4,7,10-trioxa-1,13-tridecanediamine for enhanced culturing and migration of bovine aortic endothelial cells.

Plasma surface modification is an effective method for changing material properties to control cell behavior on a surface. This study investigates the efficiency of a plasma polymerized 4,7,10-trioxa-1,13-tridecanediamine (ppTTDDA) film coated on a polystyrene (PS) Petri dish, which is a biocompatible surface with carbon- and oxygen-based chemical species. The adhesion, proliferation, and migration properties of bovine aortic endothelial cells (BAECs) were profoundly enhanced in the ppTTDDA-coated PS Petri dishes without extracellular matrix (ECM) proteins, when compared with the uncoated PS Petri dishes. These observations indicate that ppTTDDA-coated PS Petri dishes can directly interact with cells, regardless of cell adhesion molecules. The increased cell affinity was attributed to the high concentration of carboxyl group on the surface of the ppTTDDA film. Such a carboxyl surface showed an excellent ability to promote culturing of BAECs. Plasma surface modification techniques are effective in improving biocompatibility and provide a surface environment for cell culture.

Reactive-oxygen-species-mediated mechanism for photoinduced antibacterial and antiviral activities of Ag3PO4.

Cubic-shaped Ag3PO4 crystals with a mean size of 1 µm were synthesized by a precipitation method from a mixed solution of AgNO3, Na2HPO4, and triethanolamine. The antibacterial activities against Escherichia coli, Listeria innocua, and Pseudomonas syringae DC3000 in both the absence and presence of Ag3PO4 under dark conditions and in the presence of Ag3PO4 under red-light (625 nm) and blue-light (460 nm) irradiation were examined. The concentrations of reactive oxygen species (ROS) were also measured in the antibacterial action of the Ag3PO4 against Escherichia coli. The photoinduced enhancement of the Ag3PO4 antibacterial activity under blue-light irradiation is explained by the formation of ROS during the antibacterial action of the Ag3PO4. Moreover, the antiviral activity of Ag3PO4 against amphotropic 10A1 murine leukemia virus enhanced under blue-light irradiation via ROS production. These results provide an insight into extended bio-applications of Ag3PO4.

Antiatherogenic Effect of Resveratrol Attributed to Decreased Expression of ICAM-1 (Intercellular Adhesion Molecule-1).

Objective- Increasing evidence shows that resveratrol has antiatherogenic effects, but its underlying mechanisms are unknown. Thus, we evaluated the molecular mechanisms underlying the antiatherogenic effect of resveratrol. Approach and Results- Using the previously established mouse atherosclerosis model of partial ligation of the left carotid artery, we evaluated the role of resveratrol in antiatherosclerosis. We attempted to determine the mechanisms associated with focal adhesions using vascular endothelial cells. The results showed that resveratrol stimulated focal adhesion kinase cleavage via resveratrol-increased expression of lactoferrin in endothelial cells. Furthermore, we found that an N-terminal focal adhesion kinase fragment cleaved by resveratrol contained the FERM (band 4.1, ezrin, radixin, and moesin)-kinase domain. Furthermore, resveratrol inhibited lipopolysaccharide-stimulated adhesion of THP-1 human monocytes by decreased expression of ICAM-1 (intercellular adhesion molecule-1). A decreased ICAM-1 level was also observed in the left carotid artery of mice treated with resveratrol. To understand the relationship between resveratrol-induced antiinflammation and focal adhesion disruption, endothelial cells were transfected with FERM-kinase. Ectopically expressed FERM-kinase, the resveratrol-cleaved focal adhesion kinase fragment, was found in the nuclear fraction and inhibited the transcription level of icam-1 via the Nrf2 (nuclear factor erythroid 2-related factor 2)-antioxidant response element complex. Finally, ectopically expressed FERM-kinase blocked tumor necrosis factor-α- or IL- (interleukin) stimulated monocytic binding to endothelial cells. Conclusions- Our results show that resveratrol inhibits the expression of ICAM-1 via transcriptional regulation of the FERM-kinase and Nrf2 interaction, thereby blocking monocyte adhesion. These suppressive effects on the inflammatory mechanism suggest that resveratrol delayed the onset of atherosclerosis.

Pinosylvin enhances leukemia cell death via down-regulation of AMPKα expression.

Resveratrol at high concentrations (50-100 µmol/L) is known to induce cell death in leukemia cells. Here, we investigated whether pinosylvin, a resveratrol analogue, induced cell death in leukemia cells. Cell death was found to be markedly elevated by 50- to 100-µmol/L pinosylvin in THP-1 and U937 cells. It was also shown that pinosylvin induced caspase-3 activation, flip-flop of phosphatidylserine, LC3-II accumulation, LC3 puncta, and p62 degradation in both THP-1 and U937 cells. These data indicate that pinosylvin-induced cell death may occur through apoptosis and autophagy. In addition, we showed that pinosylvin down-regulates AMP-activated protein kinase α1 (AMPKα1) in leukemia cells. Therefore, we correlated AMPKα1 down-regulation and leukemia cell death. AMPKα1 inhibition appeared to decrease pinosylvin-induced apoptosis and autophagy in leukemia cells, implying that AMPK is a key regulator of leukemia cell death. Moreover, we found that both pinosylvin-induced autophagy and apoptotic progress were reduced in AMPKα1-overexpressed leukemia cells, when compared with vector-transfected cells. Cell death was elevated by AMPKα1 overexpression, whereas pinosylvin-induced cell death was markedly decreased by caspase-3 inhibitors or autophagy inhibitors. These results suggest that pinosylvin-induced depletion of AMPKα1 enhances cell death via apoptosis and autophagy in leukemia cells.

Pinosylvin exacerbates LPS-induced apoptosis via ALOX 15 upregulation in leukocytes.

Pinosylvin is known to have anti-inflammatory activity in endothelial cells. In this study, we found that pinosylvin had a pro-apoptotic activity in lipopolysaccharide (LPS)-preconditioned leukocytes. This finding suggests that pinosylvin has an effect on the resolution of inflammation. To understand the detailed mechanism, we examined if pinosylvin enhances cyclooxygenase (COX) or lipoxygenase (LOX) activity in THP-1 and U937 cells. LOX activity was found to be markedly increased by pinosylvin, whereas COX activity was not altered. Furthermore, we found that pinosylvin enhanced both levels of ALOX 15 mRNA and protein, implying that LOX activity, elevated by pinosylvin, is attributed to upregulation of ALOX 15 expression. From this cell signaling study, pinosylvin appeared to promote phosphorylations of ERK and JNK. ERK or JNK inhibitors were found to attenuate ALOX 15 expression and LPS-induced apoptosis promoted by pinosylvin. In conclusion, pinosylvin enhances the apoptosis of LPSpreconditioned leukocytes by up-regulating ALOX 15 expression through ERK and JNK. These findings suggest that pinosylvin may induce the resolution of inflammation. [BMB Reports 2018; 51(6): 302-307].

Atherosclerosis is exacerbated by chitinase-3-like-1 in amyloid precursor protein transgenic mice.

Although the important role of amyloid precursor protein (APP) in vascular diseases associated with Alzheimer's disease (AD) has been demonstrated, the underlying molecular mechanisms and physiological consequences are unclear. We aimed to evaluate vascular inflammation and atherosclerosis in Swedish mutant of human APP transgenic (APPsw-Tg) and ApoE-/-/APPsw-Tg mice. We also aimed to explore the mechanisms underlying any changes observed in these mice compared with non-Tg controls. Methods: The transgenic and non-Tg mouse strains were subjected to partial ligation of the left carotid artery to induce atherosclerotic changes, which were measured using histological approaches, immunohistochemistry, quantitative polymerase chain reaction, and gene expression microarrays. Results: Our results showed increased vascular inflammation, arterial wall thickness, and atherosclerosis in APPsw-Tg and ApoE-/-/APPsw-Tg mice. We further found that the expression of chitinase-3-like-1 (Chi3l1) is increased in the APPsw-Tg mouse artery and Chi3l1 mediates endothelial cell (EC) inflammation and vascular smooth muscle cell (VSMC) activation, which in turn exacerbates atherosclerosis. In addition, using two publicly available microarray datasets from the dorsolateral prefrontal cortex of people with AD and unaffected controls as well as inflamed human umbilical vein endothelial cells, we found that Chi3l1 and associated inflammatory gene were significantly associated with AD, evaluated by co-expression network analysis and functional annotation. Knockdown of Chi3l1 in the arterial endothelium in vivo suppressed the development of atherosclerosis. We also show that microRNA 342-3p (miR-342-3p) inhibits EC inflammation and VSMC activation through directly targeting Chi3l1, and that APPsw increased Chi3l1 expression by reducing miR-342-3p expression in the arterial endothelium, promoting atherosclerosis. Conclusion: Our findings suggest that targeting Chi3l1 might provide new diagnostic and therapeutic strategies for vascular diseases in patients with AD.

Copper Ion from Cu2O Crystal Induces AMPK-Mediated Autophagy via Superoxide in Endothelial Cells.

Copper is an essential element required for a variety of functions exerted by cuproproteins. An alteration of the copper level is associated with multiple pathological conditions including chronic ischemia, atherosclerosis and cancers. Therefore, copper homeostasis, maintained by a combination of two copper ions (Cu(+) and Cu(2+)), is critical for health. However, less is known about which of the two copper ions is more toxic or functional in endothelial cells. Cubic-shaped Cu2O and CuO crystals were prepared to test the role of the two different ions, Cu(+) and Cu(2+), respectively. The Cu2O crystal was found to have an effect on cell death in endothelial cells whereas CuO had no effect. The Cu2O crystals appeared to induce p62 degradation, LC3 processing and an elevation of LC3 puncta, important processes for autophagy, but had no effect on apoptosis and necrosis. Cu2O crystals promote endothelial cell death via autophagy, elevate the level of reactive oxygen species such as superoxide and nitric oxide, and subsequently activate AMP-activated protein kinase (AMPK) through superoxide rather than nitric oxide. Consistently, the AMPK inhibitor Compound C was found to inhibit Cu2O-induced AMPK activation, p62 degradation, and LC3 processing. This study provides insight on the pathophysiologic function of Cu(+) ions in the vascular system, where Cu(+) induces autophagy while Cu(2+) has no detected effect.

An implantable, batteryless, and wireless capsule with integrated impedance and pH sensors for gastroesophageal reflux monitoring.

In this study, a device for gastroesophageal reflux disease (GERD) monitoring has been prototyped. The system consists of an implantable, batteryless and wireless transponder with integrated impedance and pH sensors; and a wearable, external reader that wirelessly powers up the transponder and interprets the transponded radio-frequency signals. The transponder implant with the total size of 0.4 cm × 0.8 cm × 3.8 cm harvests radio frequency energy to operate dual-sensor and load-modulation circuitry. The external reader can store the data in a memory card and/or send it to a base station wirelessly, which is optional in the case of multiple-patient monitoring in a hospital or conducting large-scale freely behaving animal experiments. Tests were carried out to verify the signal transduction reliability in different situations for antenna locations and orientation. In vitro, experiments were conducted in a mannequin model by positioning the sensor capsule inside the wall of a tube mimicking the esophagus. Different liquids with known pH values were flushed through the tube creating reflux episodes and wireless signals were recorded. Live pigs under anesthesia were used for the animal models with the transponder implant attached on the esophageal wall. The reflux episodes were created while the sensor data were recorded wirelessly. The data were compared with those recorded independently by a clinically used wireless pH sensor capsule placed next to our implant transponder. The results showed that our transponder detected every episode in both acid and nonacid nature, while the commercial pH sensor missed events that had similar, repeated pH values, and failed to detect pH values higher than 10. Our batteryless transponder does not require a battery thus allowing longer diagnosis and prognosis periods to monitor drug efficacy, as well as providing accurate assessment of GERD symptoms.

A wireless system for monitoring transcranial motor evoked potentials.

Intraoperative neurophysiological monitoring (IONM) is commonly used as an attempt to minimize neurological morbidity from operative manipulations. The goal of IONM is to identify changes in the central and peripheral nervous system function prior to irreversible damage. Intraoperative monitoring also has been effective in localizing anatomical structures, including peripheral nerves and sensorimotor cortex, which helps guide the surgeon during dissection. As part of IONM, transcranial motor evoked potentials (TcMEPs), and somatosensory evoked potentials (SSEPs) are routinely monitored. However, current wired systems are cumbersome as the wires contribute to the crowded conditions in the operating room and in doing so not only it limits the maneuverability of the surgeon and assistants, but also places certain demand in the total anesthesia required during surgery, due to setup preoperative time needed for proper electrode placement, due to the number and length of the wires, and critical identification of the lead wires needed for stimulation and recording. To address these limitations, we have developed a wireless TcMEP IONM system as a first step toward a multimodality IONM system. Bench-top and animal experiments in rodents demonstrated that the wireless method reproduced with high fidelity, and even increased the frequency bandwidth of the TcMEP signals, compared to wired systems. This wireless system will reduce the preoperative time required for IONM setup, add convenience for surgical staff, and reduce wire-related risks for patients during the operation.