Associations of chronic conditions, APOE4 allele, stress factors, and health behaviors with self-rated health

BackgroundSelf-rated health (SRH) has been widely used to measure the overall health status of older adults. Research has shown that SRH is determined by a large array of factors, such as chronic disease conditions, genetic markers (e.g., Apolipoprotein E, APOE, NM_000041), stress factors, and health behaviors. However, few studies have incorporated these factors simultaneously in the analytic framework of SRH. The aim of this study is to examine the associations of these four sets of factors with SRH.MethodsUsing a dataset from a population-based, random-cluster survey of 1,005 elderly respondents aged 54–91 conducted in Taiwan in 2000, we use logistic regressions to examine associations of chronic health conditions, the APOE4 allele stress factors, and health behaviors with SRH. The four disease conditions include diabetes, heart diseases, gastric ulcers, and chronic obstructive pulmonary disease. Stress factors are measured by traumatic events (having an earthquake-damaged house) and chronic life stress (financial difficulty). Health behaviors include smoking, drinking alcohol, vegetable and fruit intake, daily milk intake, and physical exercise.ResultsDiabetes, heart diseases, gastric ulcers, and chronic obstructive pulmonary disease are found to be associated with 2.63 (95 % CI: 1.75–3.95), 1.72 (95 % CI: 1.15–2.58), 1.94 (95 % CI: 1.35–2.80), and 2.54 (95 % CI: 1.66–3.92) odds ratios of poor SRH. The APOE4 allele is found to be significantly associated with poor SRH with odd ratio of 1.58 (95% CI: 1.02–2.41). Financial difficulty is associated with increased likelihood of poor SRH, with odds ratios of 1.76 (95 % CI: 1.22–2.54) Doing exercise more than 5 times per week are associated with reduced likelihood of poor SRH by 44% (odds ratio is 0.56, 95% CI: 0.39–1.82). The interaction term between gender and gastric ulcer showed that the impact of gastric ulcer on SRH is more pronounced in women than in men, with an odds ratio of 2.63 (95 % CI: 1.24–5.58).ConclusionsChronic conditions and the APOE4 allele are significantly associated with increased likelihood of reporting poor health, and the associations appear differently among women and men. To better understand the mechanism of how people self-assess their overall health, chronic conditions and genetic components should be considered together with conventional factors such as life stress and health behaviors

Protective effect of dehydroandrographolide on obstructive cholestasis in bile duct-ligated mice

Background: Dehydroandrographolide (DA) is the main contributor to the therapeutic properties of the medicinal plant Andrographis paniculata (AP). However, it is unknown whether DA has a hepatoprotective effect on obstructive cholestasis in mice and humans. Methods: We administered DA to mice for 5 days prior to bile duct ligation (BDL) and for the 7 days. Liver function markers, liver histology and necrosis, compensatory responses of hepatocytes, liver fibrosis and the expression of hepatic fibrogenesis markers were evaluated in BDL mice and/or human LX-2 cells. Results: Mice treated with DA demonstrated lower levels of serum alanine transarninase (ALT), milder liver damage, liver necrosis and fibrosis formation than in vehicle control with carboxymethylcellulose (CMC) mice after BDL. DA treatment also enhanced the Mrp3 expression of hepatocytes but not Mrp4 following BDL. Further, DA treatment in BDL mice significantly reduced liver mRNA and/or protein expression of Tgf-β, Col1a1, α-Sma and Mmp2. This result was also supported by hydroxyproline analysis. The molecular mechanisms of DA treatment were also assessed in human hepatic stellate cell line (LX-2 cell). DA treatment significantly inhibited Tgf-β-induced Col1a1, Mmp2 and α-Sma expression in human LX-2 cells. These data suggested that DA treatment reduced liver damage through development of a hepatic adaptive response and inhibition of the activation of HSCs, which led to a reduction in liver fibrosis formation in BDL mice. Conclusions: DA treatment protected against liver damage and fibrosis following BDL and might be an effective therapy for extrahepatic cholestasis due to bile duct obstruction

Anti-Inflammatory Activity of Dehydroandrographolide by TLR4/NF-κB Signaling Pathway Inhibition in Bile Duct-Ligated Mice

Background/Aims: Clinically, biliary obstruction is often accompanied by progressive inflammation. Dehydroandrographolide (DA) possesses anti-inflammatory properties. However, the anti-inflammatory activities of DA in cholestatic liver injury remain unclear. Methods: Mice were administered with DA by intraperitoneal injection after bile duct ligation (BDL) on day 1. Then mice were subjected to an ileocecal vein injection of lipopolysaccharide (LPS). Liver function markers, histology, pro-inflammatory cytokine levels, NF-κB activation and fibrosis formation were evaluated in BDL mice with LPS. LPS binding to primary Kupffer cells was examined by high-content cytometers. Results: DA was shown to greatly lower initially higher than normal levels of alanine aminotransferase (ALT) and total bilirubin (TBIL) in the serum and liver of BDL mice with LPS. DA exerted hepatic protective effects that were also confirmed by prolonged survival of BDL mice with LPS. Liver histopathology showed reduced inflammatory cellular infiltration, bile duct proliferation, and biliary necrosis with DA treatment. Furthermore, DA reduced the expression levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in liver tissue and plasma and showed decreased NF-κB activation in BDL mice with LPS. DA could prevent LPS binding to primary Kupffer cells in the normal liver and BDL mice liver. DA also suppressed LPS-stimulated inflammatory responses by blocking the interaction between LPS and TLR4 in primary Kupffer cells and human LX-2 cells, thereby inhibiting NF-κB activation. Conclusion: DA inhibition of inflammation against liver damage following BDL with LPS may be a promising agent for the treatment of cholestatic liver injury

Protective Effect of Hydrogen on Sodium Iodate-Induced Age-Related Macular Degeneration in Mice

Oxidative stress is one of the main causes of AMD. Hydrogen has anti-oxidative stress and apoptotic effects on retinal injury. However, the effect of hydrogen on AMD is not clear. In this study, fundus radiography, OCT, and FFA demonstrated that HRW reduced the deposition of drusen-like structures in RPE layer, prevented retina from thinning and leakage of ocular fundus vasculature induced by NaIO3. ERG analysis confirmed that HRW effectively reversed the decrease of a-wave and b-wave amplitude in NaIO3-mice. Mechanistically, HRW greatly reduced the oxidative stress reaction through decreased MDA levels, increased SOD production, and decreased ROS content. The OGG1 expression was downregulated which is a marker of oxidative stress. Involvement of oxidative stress was confirmed using oxidative stress inhibitor ALCAR. Moreover, oxidative stress reaction was associated with expression of Sirt1 level and HRW significantly inhibited the downregulation of Sirt1 expression. This result was further confirmed with AICAR which restore Sirt1 expression and activity. In addition, NaIO3-induced retinal damage was related to apoptosis via caspase 8 and caspase 9, but not the caspase 3 pathways, which led to upregulation of Bax and p53, downregulation of Bcl-2, and increase in Jc-1-positive cells in mice. However, HRW effectively reversed these effects that apoptosis induced. These results suggest that HRW protects retinal functions against oxidative stress injury through inhibiting downregulation of Sirt1 and reducing retinal apoptosis. Therefore, we speculated that hydrogen administration is a promising treatment for AMD therapy

An Engineered Arginase FC Protein Inhibits Tumor Growth In Vitro

Arginine is a semiessential amino acid required for the growth of melanoma and hepatocellular carcinoma, and the enzymatic removal of arginine by pegylated arginine deiminase (ADI) or arginase is being tested clinically. Here, we report a genetically engineered arginase FC fusion protein exhibiting a prolonged half-life and enhanced efficacy. The use of this enzyme to treat different tumor lines both inhibited cell proliferation and impaired cellular migration in vitro and in vivo. Our data reinforce the hypothesis that nutritional depletion is a key strategy for cancer treatment

Computed Tomography Simulation Using Supertoroids

Analytic simulation in computed tomography(CT) generates projection data for evaluating and improving CT image reconstruction algorithms and has played an important role in the research and development of x-ray CT. The simulation is desired to be as realistic as possible while the computation needs to be efficient and accurate. Early primitive equation-based phantoms such as Shepp-Logan and FORBILD use only boxes, cylinders, and quadrics to simulate body parts. The superquadrics have been used in Computer Graphics since 1980\u27s, and in CT since 1990\u27s. While their more complex shapes make them more realistic in simulation, the difficulties in solving their equations increase dramatically, which restricts their use, especially in ray-tracing and x-ray transform. Zhu et al. developed an algorithm for ray-intersecting the superellipsoid and used it to build a thorax phantom. No algorithms for ray-intersecting the supertoroid, however, are known up to now to the best of our knowledge. In this paper we propose such an algorithm and use it in computation of x-ray transform. The algorithm was tested by a phantom consisting of the top portion of vertebrae and a few ribs. Cone-beam data were produced from the phantom, and then used to reconstruct the phantom

High-Degree Polynomial Models for CT Simulation

The power and flexibility of polynomial surfaces are unleashed when their degrees are no longer restricted to four or lower, as they are used in early CT phantoms. They have proved useful and appropriate for geometric simulation of human and animal anatomy. In this paper a general algorithm is presented for the x-ray transform of any polynomial surface, as long as its ray-surface intersection equation is implemented on the computer. A versatile and powerful polynomial utility C++ class is created to simplify the implementation. Three groups of surfaces are implemented and applied to build a heart phantom closely simulating the Visible Man\u27s heart. The x-ray transform algorithm is tested and verified by the successful reconstruction of the heart phantom