Effects of Ixeris Chinensis (Thunb.) Nakai boiling water extract on hepatitis B viral activity and hepatocellular carcinoma

Background: Hepatitis B virus (HBV) infection and hepatocellular carcinoma are major diseases that affect the Taiwanese population. Therefore, the development of an alternative herbal medicine that can effectively treat these diseases is a research target. In this study, we tested Ixeris Chinensis (Thunb.) Nakai boiling water extract (ICTN BWE) in vitro and analysed its effects on the HBV and liver cancer.Materials and Methods: We used a human liver cancer cell line (Hep3B, a cell line that continuously secretes HBV particles into a medium) as an experimental model for the screening of various ICTN BWE concentrations and their effects on the HBV in vitro.Results: Our results showed that 75 μg/mL ICTN BWE downregulated the relative expression of the hepatitis B virus surface antigens (HBsAg) to 77.1%. Using the human liver cancer cell lines HuH-7 and HepG2, and 3-(4,5- dimethylthiazol-zyl)-2,5-diphenyl tetrazolium bromide (MTT) and tumour clonogenic assays, we then showed that ICTN BWE inhibits hepatocellular carcinoma growth.Conclusion: Fluorescent microscopy of DAPI(4',6-Diamidino-2-phenylindole)-stained nuclei and DNA fragmentation assays confirmed the inhibitory effects of ICTN BWE on liver tumour cell growth through induction of apoptosis.Keywords: herbal medicine, Ixeris Chinensis (Thunb.) Nakai, antihepatocellular carcinoma, apoptosis, antihepatitis B viru

Dual Drug-Loaded Biofunctionalized Amphiphilic Chitosan Nanoparticles: Enhanced Synergy between Cisplatin and Demethoxycurcumin against Multidrug-Resistant Stem-Like Lung Cancer Cells

Lung cancer kills more humans than any other cancer and multidrug resistance (MDR) in cancer stem-like cells (CSC) is emerging as a reason for failed treatments. One concept which addresses this root cause of treatment failure is the utilization of nanoparticles to simultaneously deliver dual drugs to cancer cells with synergistic performance, easy to envision - hard to achieve. It is challenging to simultaneously load drugs of highly different physicochemical properties into one nanoparticle, release kinetics may differ between drugs and general requirements for biomedical nanoparticles apply. Here self-assembled nanoparticles of amphiphilic carboxymethyl-hexanoyl chitosan (CHC) were shown to present nano-microenvironments enabling simultaneous loading of hydrophilic and hydrophobic drugs. This was expanded into a dual-drug nano-delivery system to treat lung CSC. CHC nanoparticles were loaded/chemically modified with the anticancer drug cisplatin and the MDR-suppressing Chinese herbal extract demethoxycurcumin, followed by biofunctionalization with CD133 antibody for enhanced uptake by lung CSC, all in a feasible one-pot preparation. The nanoparticles were characterized with regard to chemistry, size, zeta potential and drug loading/release. Biofunctionalized and non-functionalized nanoparticles were investigated for uptake by lung CSC. Subsequently the cytotoxicity of single and dual drugs, free in solution or in nanoparticles, was evaluated against lung CSC at different doses. From the dose response at different concentrations the degree of synergy was determined through Chou-Talalay's Plot. The biofunctionalized nanoparticles promoted synergistic effects between the drugs and were highly effective against MDR lung CSC. The efficacy and feasible one-pot preparation suggest preclinical studies using relevant disease models to be justified

Deep Autoencoder for Combined Human Pose Estimation and body Model Upscaling

We present a method for simultaneously estimating 3D human pose and body shape from a sparse set of wide-baseline camera views. We train a symmetric convolutional autoencoder with a dual loss that enforces learning of a latent representation that encodes skeletal joint positions, and at the same time learns a deep representation of volumetric body shape. We harness the latter to up-scale input volumetric data by a factor of $4 \times$, whilst recovering a 3D estimate of joint positions with equal or greater accuracy than the state of the art. Inference runs in real-time (25 fps) and has the potential for passive human behaviour monitoring where there is a requirement for high fidelity estimation of human body shape and pose

Angiotensin II type 1 receptor-dependent oxidative stress mediates endothelial dysfunction in type 2 diabetic mice

The mechanisms underlying the effect of the renin-angiotensin-aldosterone system (RAAS) inhibition on endothelial dysfunction in type 2 diabetes are incompletely understood. This study explored a causal relationship between RAAS activation and oxidative stress involved in diabetes-associated endothelial dysfunction. Daily oral administration of valsartan or enalapril at 10mg/kg/day to db/db mice for 6 weeks reversed the blunted acetylcholine-induced endothelium-dependent dilatations, suppressed the upregulated expression of angiotensin II type 1 receptor (AT1R) and NAD(P)H oxidase subunits (p22phox and p47phox), and reduced reactive oxygen species (ROS) production. Acute exposure to AT1R blocker losartan restored the impaired endothelium-dependent dilatations in aortas of db/db mice and also in renal arteries of diabetic patients (fasting plasma glucose level ≥7.0 mmol/l). Similar observations were also made with apocynin, diphenyliodonium, or tempol treatment in db/db mouse aortas. DHE fluorescence revealed an overproduction of ROS in db/db aortas which was sensitive to inhibition by losartan or ROS scavengers. Losartan also prevented the impairment of endothelium-dependent dilatations under hyperglycemic conditions that were accompanied by high ROS production. The present study has identified an initiative role of AT1R activation in mediating endothelial dysfunction of arteries from db/db mice and diabetic patients. © 2010 Mary Ann Liebert, Inc.published_or_final_versio

Counterflow dielectrophoresis for trypanosome enrichment and detection in blood

Human African trypanosomiasis or sleeping sickness is a deadly disease endemic in sub-Saharan Africa, caused by single-celled protozoan parasites. Although it has been targeted for elimination by 2020, this will only be realized if diagnosis can be improved to enable identification and treatment of afflicted patients. Existing techniques of detection are restricted by their limited field-applicability, sensitivity and capacity for automation. Microfluidic-based technologies offer the potential for highly sensitive automated devices that could achieve detection at the lowest levels of parasitemia and consequently help in the elimination programme. In this work we implement an electrokinetic technique for the separation of trypanosomes from both mouse and human blood. This technique utilises differences in polarisability between the blood cells and trypanosomes to achieve separation through opposed bi-directional movement (cell counterflow). We combine this enrichment technique with an automated image analysis detection algorithm, negating the need for a human operator

Uncoupling Protein-2 Mediates DPP-4 Inhibitor-Induced Restoration of Endothelial Function in Hypertension Through Reducing Oxidative Stress

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Expanding genotype/phenotype of neuromuscular diseases by comprehensive target capture/NGS

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Oxidative stress-dependent cyclooxygenase-2-derived prostaglandin F2α impairs endothelial function in renovascular hypertensive rats

Abstract Aims: The role of endothelium-derived contracting factors (EDCFs) in regulating renovascular function is yet to be elucidated in renovascular hypertension (RH). The current study investigated whether oxidative stress-dependent cyclooxygenase (COX)-2-derived prostaglandin F(2alpha) (PGF(2alpha)) impairs endothelial function in renal arteries of renovascular hypertensive rats (RHR). Results: Renal hypertension was induced in rats by renal artery stenosis of both kidneys using the 2-kidney 2-clip model. Acute treatment with reactive oxygen species (ROS) scavengers, COX-2 inhibitors, and thromboxane-prostanoid receptor antagonists, but not COX-1 inhibitors, improved endothelium-dependent relaxations and eliminated endothelium-dependent contractions in RHR renal arteries. Five weeks of treatment with celecoxib or tempol reduced blood pressure, increased renal blood flow, and restored endothelial function in RHRs. Increased ROS production in RHR arteries was inhibited by ROS scavengers, but unaffected by COX-2 inhibitors; whereas increased PGF(2alpha) release was reduced by both ROS scavengers and COX-2 inhibitors. ROS also induced COX-2-dependent contraction in RHR renal arteries, which was accompanied by the release of COX-2-derived PGF(2alpha). Further, chronic tempol treatment reduced COX-2 and BMP4 upregulation, p38MAPK phosphorylation, and the nitrotyrosine level in RHR renal arteries. Conclusion: These findings demonstrate the functional importance of oxidative stress, which serves as an initiator of increased COX-2 activity, and that COX-2-derived PGF(2alpha) plays an important role in mediating endothelial dysfunction in RH. Innovation: The current study, thus, suggests that drugs targeting oxidative stress-dependent COX-2-derived PGF(2alpha) may be useful in the prevention and management of RH. Antioxid. Redox Signal. 16, 363-373.published_or_final_versio

Materials Characterization Using Acoustic Nonlinearity Parameters and Harmonic Generation: Effects of Crystalline and Amorphous Structures

The importance of nonlinearity in the description of material behavior is gaining widespread attention. Nonlinearity plays a major, if not dominating, role in a number of material properties. For example, properties that are important in engineering design such as thermal expansion or the pressure dependence of optical refraction are inherently nonlinear [1]. New assembley techniques such as the use of ultrasonic gauges to determine the loading of critical fasteners depend upon nonlinear properties of the fasteners [2]. Areas of considerable fundamental interest in nonlinearity include lattice dynamics [3], radiation stress in solids [4,5], and nonlinear optics [6