Acupuncture Point Stimulation Treatments Combined With Conventional Treatment in Chronic Obstructive Pulmonary Disease: A Systematic Review and Network Meta-Analysis.

Background: Chronic obstructive pulmonary disease (COPD), which is a disease characterized by dyspnea, cough, and respiratory symptoms, leading to impaired health-related quality of life (HRQL) and exercise capacity, is highly prevalent worldwide. Some studies demonstrated that acupuncture point stimulation treatments (APSTs) are effective and safe in treating patients with COPD. The aim of this systematic review and network meta-analysis is to analyze the effects on HRQL and FEV1% predicted of diverse APSTs in treating patients with COPD. Materials and Methods: We searched seven electronic databases. Randomized controlled trials (RCTs) with stable COPD patients comparing APSTs and conventional treatment (Tx) were included. The primary outcome was HRQL measured by COPD Assessment Test or St. George's Respiratory Questionnaire. The secondary outcome was FEV1% predicted. We performed random effect network meta-analysis using a consistency model. Results: This network meta-analysis analyzed 21 RCTs with 1,577 stable COPD participants. In comparison with Tx, acupressure massage (AM) + Tx [-5.11; 95% confidence interval (CI), -6.65 to -3.57] was the most effective intervention in improving HRQL, followed by moxibustion (Mx) + Tx (-2.86; 95% CI, -3.86 to -1.86). Moreover, in comparison with Tx, Mx + Tx (7.79; 95% CI, 2.16 to 13.42) was the most effective intervention in improving FEV1% predicted, followed by acupuncture (A) + Tx (5.79; 95% CI, 2.90 to 8.68). Conclusions: Combined interventions (APSTs + Tx) are more effective than single intervention in improving both HRQL and FEV1% predicted. AM, Mx, and A can be considered effective non-pharmacological complementary interventions in treating patients with COPD under Tx.

Modulation of human platelet activation and in vivo vascular thrombosis by columbianadin: regulation by integrin αIIbß3 inside-out but not outside-in signals.

BACKGROUND: Columbianadin (CBN) is one of the main coumarin constituents isolated from Angelica pubescens. The pharmacological value of CBN is well demonstrated, especially in the prevention of several cancers and analgesic activity. A striking therapeutic target for arterial thrombosis is inhibition of platelet activation because platelet activation significantly contributes to these diseases. The current study examined the influence of CBN on human platelet activation in vitro and vascular thrombotic formation in vivo. METHODS: Aggregometry, immunoblotting, immunoprecipitation, confocal microscopic analysis, fibrin clot retraction, and thrombogenic animals were used in this study. RESULTS: CBN markedly inhibited platelet aggregation in washed human platelets stimulated only by collagen, but was not effective in platelets stimulated by other agonists such as thrombin, arachidonic acid, and U46619. CBN evidently inhibited ATP release, intracellular ([Ca2+]i) mobilization, and P-selectin expression. It also inhibited the phosphorylation of phospholipase C (PLC)γ2, protein kinase C (PKC), Akt (protein kinase B), and mitogen-activated protein kinases (MAPKs; extracellular signal-regulated kinase [ERK] 1/2 and c-Jun N-terminal kinase [JNK] 1/2, but not p38 MAPK) in collagen-activated platelets. Neither SQ22536, an adenylate cyclase inhibitor, nor ODQ, a guanylate cyclase inhibitor, reversed the CBN-mediated inhibition of platelet aggregation. CBN had no significant effect in triggering vasodilator-stimulated phosphoprotein phosphorylation. Moreover, it markedly hindered integrin αIIbß3 activation by interfering with the binding of PAC-1; nevertheless, it had no influences on integrin αIIbß3-mediated outside-in signaling such as adhesion number and spreading area of platelets on immobilized fibrinogen as well as thrombin-stimulated fibrin clot retraction. Additionally, CBN did not attenuate FITC-triflavin binding or phosphorylation of proteins, such as integrin ß3, Src, and focal adhesion kinase, in platelets spreading on immobilized fibrinogen. In experimental mice, CBN increased the occlusion time of thrombotic platelet plug formation. CONCLUSION: This study demonstrated that CBN exhibits an exceptional activity against platelet activation through inhibition of the PLCγ2-PKC cascade, subsequently suppressing the activation of Akt and ERKs/JNKs and influencing platelet aggregation. Consequently, this work provides solid evidence and considers that CBN has the potential to serve as a therapeutic agent for the treatment of thromboembolic disorders.

Oridonin Attenuates Lipopolysaccharide-Induced ROS Accumulation and Inflammation in HK-2 Cells.

Renal tubulointerstitial inflammation plays an important role in chronic kidney disease (CKD). Inflammation reduction is a good strategy to combat CKD. Oridonin, an ent-kaurane diterpenoid isolated from Rabdosia rubescens (Donglingcao), is considered as an effective natural candidate for the treatment of anti-inflammatory, antiviral, and antibacterial activities, including liver fibrosis and many tumors; however, no study has demonstrated its effect on lipopolysaccharide- (LPS-) induced renal inflammation. To investigate the anti-inflammatory effects of oridonin on human renal proximal tubular epithelial cells (HK-2 cells), the expression levels of c-Jun N-terminal kinase (JNK) and reactive oxygen species (ROS) were evaluated by Western blot analysis and 2',7'-dichlorofluorescein diacetate (DCF-DA) staining, respectively. The level of intracellular ROS increased in a dose-dependent manner following LPS treatment, whereas oridonin inhibited this effect, suggestive of its ability to prevent ROS accumulation. As the mitogen-activated protein kinase (MAPK) family of enzymes plays an important role in physiological responses, we examined the activation of JNK by Western blotting and found that oridonin attenuated LPS-induced JNK phosphorylation. Oridonin also attenuated RAW 264.7 cell chemotaxis towards LPS-treated HK-2 cells. Taken together, oridonin protected against LPS-induced inflammation including ROS accumulation, JNK activation, NF-κB nuclear translocation in HK-2 cells, and functionally blocked macrophage chemotaxis towards LPS-treated HK-2 cells. Oridonin may exhibit therapeutic potential by the anti-inflammation effect in LPS-treated HK-2 cells.

Suppression of Human Platelet Activation via Integrin αIIbß3 Outside-In Independent Signal and Reduction of the Mortality in Pulmonary Thrombosis by Auraptene.

Auraptene is the most abundant coumarin derivative from plants. The pharmacological value of this compound has been well demonstrated, especially in the prevention of cancer and neurodegenerative diseases. Platelet activation is a major factor contributing to arterial thrombosis. Thus, this study evaluated the influence of auraptene in platelet aggregation and thrombotic formation. Auraptene inhibited platelet aggregation in human platelets stimulated with collagen only. However, auraptene was not effective in inhibiting platelet aggregation stimulated with thrombin, arachidonic acid, and U46619. Auraptene also repressed ATP release, [Ca2+]i mobilization, and P-selectin expression. Moreover, it markedly blocked PAC-1 binding to integrin αIIbß3. However, it had no influence on properties related to integrin αIIbß3-mediated outside-in signaling, such as the adhesion number, spreading area of platelets, and fibrin clot retraction. Auraptene inhibited the phosphorylation of Lyn-Fyn-Syk, phospholipase Cγ2 (PLCγ2), protein kinase C (PKC), Akt, and mitogen-activated protein kinases (MAPKs; extracellular-signal-regulated kinase (ERK1/2), and c-Jun N-terminal kinase (JNK1/2), but not p38 MAPK). Neither SQ22536, an adenylate cyclase inhibitor, nor ODQ, a guanylate cyclase inhibitor, reversed the auraptene-mediated inhibition of platelet aggregation. Auraptene reduced mortality caused by adenosine diphosphate (ADP)-induced pulmonary thromboembolism. In conclusion, this study provides definite evidence that auraptene signifies a potential therapeutic agent for preventing thromboembolic disorders.

Interactions of BDNF Val66Met Polymorphism and Menstrual Pain on Brain Complexity.

The irregularity and uncertainty of neurophysiologic signals across different time scales can be regarded as neural complexity, which is related to the adaptability of the nervous system and the information processing between neurons. We recently reported general loss of brain complexity, as measured by multiscale sample entropy (MSE), at pain-related regions in females with primary dysmenorrhea (PDM). However, it is unclear whether this loss of brain complexity is associated with inter-subject genetic variations. Brain-derived neurotrophic factor (BDNF) is a widely expressed neurotrophin in the brain and is crucial to neural plasticity. The BDNF Val66Met single-nucleotide polymorphism (SNP) is associated with mood, stress, and pain conditions. Therefore, we aimed to examine the interactions of BDNF Val66Met polymorphism and long-term menstrual pain experience on brain complexity. We genotyped BDNF Val66Met SNP in 80 PDM females (20 Val/Val, 31 Val/Met, 29 Met/Met) and 76 healthy female controls (25 Val/Val, 36 Val/Met, 15 Met/Met). MSE analysis was applied to neural source activity estimated from resting-state magnetoencephalography (MEG) signals during pain-free state. We found that brain complexity alterations were associated with the interactions of BDNF Val66Met polymorphism and menstrual pain experience. In healthy female controls, Met carriers (Val/Met and Met/Met) demonstrated lower brain complexity than Val/Val homozygotes in extensive brain regions, suggesting a possible protective role of Val/Val homozygosity in brain complexity. However, after experiencing long-term menstrual pain, the complexity differences between different genotypes in healthy controls were greatly diminished in PDM females, especially in the limbic system, including the hippocampus and amygdala. Our results suggest that pain experience preponderantly affects the effect of BDNF Val66Met polymorphism on brain complexity. The results of the present study also highlight the potential utilization of resting-state brain complexity for the development of new therapeutic strategies in patients with chronic pain.

Novel Therapeutic Agent against Platelet Activation In Vitro and Arterial Thrombosis In Vivo by Morin Hydrate.

Morin hydrate, a bioactive flavonoid, has been proven to prevent inflammation and apoptosis of cells. Flavonoids can reduce the risk of cardiovascular diseases, in which platelet activation plays a major role. This study investigated the effect of morin hydrate on platelet activation in vitro and in vivo. Morin hydrate markedly inhibited platelet aggregation stimulated by collagen in human platelets but not that stimulated by other agonists. In collagen-activated platelets, morin hydrate inhibited adenosine triphosphate (ATP) release; intracellular Ca2+ mobilization; P-selectin expression; and phosphorylation of phospholipase Cγ2 (PLCγ2), protein kinase C (PKC), and Akt. In mitogen-activated protein kinase (MAPK) activation, morin hydrate evidently diminished ERK2 or JNK1 activation, except for p38 MAPK. Additionally, morin hydrate markedly reduced the OH· signals in platelet suspensions but not in the cell-free system (Fenton reaction solution). Moreover, morin hydrate substantially increased the occlusion time of thrombotic platelet plug formation but had no effect on bleeding time in mice. In conclusion, morin hydrate crucially inhibits platelet activation through inhibition of the PLCγ2⁻PKC cascade and subsequent suppression of Akt and MAPK activation, thereby ultimately inhibiting platelet aggregation. Therefore, this paper suggests that morin hydrate constitutes a novel and potential natural therapeutic product for preventing or treating thromboembolic disorders.

Difference between observed and predicted glycated hemoglobin at baseline and treatment response to vildagliptin-based dual oral therapy in patients with type 2 diabetes.

AIM: We aimed to investigate the association of difference between observed and predicted glycated hemoglobin (dopHbA1c) and HbA1c reduction after vildagliptin-based oral therapy in patients with type 2 diabetes (T2D). METHODS: This was a prospective observational study. Adults ≥ 20 years old with T2D and HbA1c ≧7% treated with oral anti-diabetic drugs (OADs) were eligible if their OADs were shifted to vildagliptin-based dual oral therapy. Fasting plasma glucose (FPG) and HbA1c were recorded at baseline, week 12, and week 24. To determine baseline dopHbA1c, a predicted HbA1c was calculated by inserting baseline FPG into a regression equation (HbA1c = FPG ∗ 0.0225 + 4.3806) developed from linear relationship between HbA1c and FPG in an independent cohort of 3239 outpatients with T2D (dopHbA1c = observed HbA1c - predicted HbA1c). Patients were assigned to low (≦0) or high (>0) dopHbA1c group according to their baseline dopHbA1c levels. The study endpoint was changes from baseline to week 24 in HbA1c levels. RESULTS: A total of 1224 patients were enrolled. Patients with a dopHbA1c >0 had a greater HbA1c reduction after vildagliptin-based dual oral therapy than those with a dopHbA1c ≦0 (-1.5 ±â€¯2.0 vs. -0.4 ±â€¯1.0%, p < 0.001). Baseline dopHbA1c was positively associated with HbA1c reduction from baseline to week 24 (ß coefficient 0.883, 95% CI 0.811 to 0.955, p < 0.001), and the association remained significant after adjustment for confounders. CONCLUSIONS: In T2D patients with an HbA1c ≧7%, a higher baseline dopHbA1c was associated with a greater HbA1c reduction after shifting to vildagliptin-based dual oral therapy.

Visualization of biosensors using enhanced surface plasmon resonances in capped silver nanostructures.

We propose a method and optical design for direct visualization of label-free detection. The system, similar to a tiny spectral analyzer, is composed of a nanostructure-based surface plasmon resonance chip, linear polarizer and 532 nm laser light source. The full-width-at-half-maximum bandwidths of the enhanced surface plasmon resonances are about 5 nm. The distribution of the transmitted light from these arrays comprises a spectral image on the chip. The qualitative and quantitative analyses of the analyte can be conducted by observing the spot shift on the chip. We tested the sensing capability of the chip. The detectable surface mass density with the naked eye is about 0.476 µg cm(-2). In addition, antigen-antibody interaction experiments are conducted to verify the surface binding measurements. A monolayer protein attached on the chip can be directly observed and the concentration levels of the analyte can be estimated with the naked eye. Such plasmonic biochips can benefit sensing applications in point-of-care diagnostics.

Self-aligned Cu etch mask for individually addressable metallic and semiconducting carbon nanotubes.

Two means to achieve high yield of individually addressable single-walled carbon nanotubes (CNTs) are developed and examined. The first approach matches the effective channel width and the density of horizontally aligned CNTs. This method can provide single CNT devices and also allows control over the average number of CNTs per channel. The second and a more deterministic approach uses self-aligned Cu-filled trenches formed in a photoresist (after Joule heating of the underlying CNT) to protect and obtain a large number of single CNT devices. Unlike electrical breakdown methods, which preserve the least conducting CNT and can leave behind CNT fragments, our approach allows the selection of the single most conducting metallic CNT from an array of as-grown CNTs with average resistance ∼14 times lower than that of as-fabricated single metallic CNTs. This method can also be used to select the best semiconducting CNT from an array and yields, on average, devices that are 15 times more conductive with 40 times higher ON/OFF ratio than those selected through electrical breakdown alone.

Resistive random access memory enabled by carbon nanotube crossbar electrodes.

We use single-walled carbon nanotube (CNT) crossbar electrodes to probe sub-5 nm memory domains of thin AlOx films. Both metallic and semiconducting CNTs effectively switch AlOx bits between memory states with high and low resistance. The low-resistance state scales linearly with CNT series resistance down to ∼10 MΩ, at which point the ON-state resistance of the AlOx filament becomes the limiting factor. Dependence of switching behavior on the number of cross-points suggests a single channel to dominate the overall characteristics in multi-crossbar devices. We demonstrate ON/OFF ratios up to 5 × 10(5) and programming currents of 1 to 100 nA with few-volt set/reset voltages. Remarkably low reset currents enable a switching power of 10-100 nW and estimated switching energy as low as 0.1-10 fJ per bit. These results are essential for understanding the ultimate scaling limits of resistive random access memory at single-nanometer bit dimensions.

Integration of type II nanorod heterostructures into photovoltaics.

High-quality epitaxial interfaces and delicate control over shape anisotropy make nanorod heterostructures (NRHs) with staggered band offsets efficient in separating and directing photogenerated carriers. Combined with versatile and scalable wet chemical means of synthesis, these salient features of NRHs are useful for improving both the performance and the cost-effectiveness of photovoltaics (PVs). However, inefficient carrier transport and extraction have imposed severe limitations, outweighing the benefits of enhanced charge separation. Hence integration of type II NRHs into PVs has thus far been unfruitful. Here, we demonstrate PVs that utilize NRHs as an extremely thin absorber between electron and hole transporting layers. In the limit approaching monolayer thickness, PVs incorporating NRHs have up to three times the short circuit current and conversion efficiency over devices made from their single-component counterparts. Comparisons between linear and curved NRHs are also made, revealing the importance of internal geometry and heterointerfacial area for enhanced contribution of charge-separated state absorption to photocurrent and in contacting charge transport layers.

Temperature and gate voltage dependent Raman spectra of single-layer graphene.

Raman spectra of electrostatically gated single-layer graphene are measured from room temperature to 560 K to sort out doping and thermally induced effects. Repeated heating cycles under Ar led to convergent first-order temperature coefficients of the G-band (χ(G) = -0.03 cm(-1)/K) and the 2D-band (χ(2D) = -0.05 cm(-1)/K) frequencies, which are independent of doping level as long as the Fermi level does not shift with temperature. While the intrinsic behavior may be different (e.g., χ(G) ∼ -0.02 cm(-1)/K near room temperature), these values appear more appropriate in describing responses of most graphene samples on SiO(2) substrates. The more negative χ(G) value than theoretical expectations may be explained by interactions with the substrate reducing the lattice thermal expansion contribution to the temperature dependence of G-band frequency. Enhanced interactions with the substrate may also be responsible for zero-charge, room-temperature G-band line width increase and 2D-band frequency downshift.

Layer-by-layer transfer of multiple, large area sheets of graphene grown in multilayer stacks on a single SiC wafer.

Here we report a technique for transferring graphene layers, one by one, from a multilayer deposit formed by epitaxial growth on the Si-terminated face of a 6H-SiC substrate. The procedure uses a bilayer film of palladium/polyimide deposited onto the graphene coated SiC, which is then mechanically peeled away and placed on a target substrate. Orthogonal etching of the palladium and polyimide leaves isolated sheets of graphene with sizes of square centimeters. Repeating these steps transfers additional sheets from the same SiC substrate. Raman spectroscopy, scanning tunneling spectroscopy, low-energy electron diffraction and X-ray photoelectron spectroscopy, together with scanning tunneling, atomic force, optical, and scanning electron microscopy reveal key properties of the materials. The sheet resistances determined from measurements of four point probe devices were found to be ∼2 kΩ/square, close to expectation. Graphene crossbar structures fabricated in stacked configurations demonstrate the versatility of the procedures.

Manifestation of Kohn anomaly in 1/f fluctuations in metallic carbon nanotubes.

Low-frequency noise in metallic single walled carbon nanotubes is shown to be strongly dependent on the Fermi level position and the applied electric field across the nanotube. Resonance-like enhancement observed near optical phonon energy only when the Fermi level lies near the Dirac point is correlated to Raman G-band softening and broadening. The results suggest that the competition between zone-center and zone-boundary phonon scattering is the underlying origin of the large enhancement and resonance-like behavior of 1/f noise.