A mitochondrial superoxide theory for oxidative stress diseases and aging

Fridovich identified CuZnSOD in 1969 and manganese superoxide dismutase (MnSOD) in 1973, and proposed ”the Superoxide Theory,” which postulates that superoxide (O₂^•−) is the origin of most reactive oxygen species (ROS) and that it undergoes a chain reaction in a cell, playing a central role in the ROS producing system. Increased oxidative stress on an organism causes damage to cells, the smallest constituent unit of an organism, which can lead to the onset of a variety of chronic diseases, such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis and other neurological diseases caused by abnormalities in biological defenses or increased intracellular reactive oxygen levels. Oxidative stress also plays a role in aging. Antioxidant systems, including non-enzyme low-molecular-weight antioxidants (such as, vitamins A, C and E, polyphenols, glutathione, and coenzyme Q₁₀) and antioxidant enzymes, fight against oxidants in cells. Superoxide is considered to be a major factor in oxidant toxicity, and mitochondrial MnSOD enzymes constitute an essential defense against superoxide. Mitochondria are the major source of superoxide. The reaction of superoxide generated from mitochondria with nitric oxide is faster than SOD catalyzed reaction, and produces peroxynitrite. Thus, based on research conducted after Fridovich’s seminal studies, we now propose a modified superoxide theory; i.e., superoxide is the origin of reactive oxygen and nitrogen species (RONS) and, as such, causes various redox related diseases and aging.     

Antihyperlipidemic activity of Allium chinense bulbs

Allium chinense is a medicinal plant and nutritional food commonly used in Eastern Asia. In this study, we investigated the in vitro antioxidant activity (scavenging of α,α-diphenyl-β-picrylhydrazyl free radical, total phenol content, reducing power, and total antioxidant activity) and constituents of various extracts from A. chinense. Moreover, we also studied the in vivo hypolipidemic effects of extracts on high-fat-diet Wistar rats. Ethanol extracts from A. chinense showed notable antioxidant activity, and its high-dose essential-oil extract both significantly reduced serum and hepatic total cholesterol, triglyceride, and low-density lipoprotein levels and increased serum high-density lipoprotein levels in high-fat-diet Wistar rats compared with those observed following treatment with the control drug probucol. Additionally, visceral fat in high-fat-diet Wistar rats was reduced. Furthermore, groups with high doses of essential-oil and residue extracts showed protective effects associated with histopathological liver alteration. These results suggested that A. chinense is a valuable plant worthy of further investigation as a potential dietary supplement or botanical drug.     

Liquid Crystalline Network Composites Reinforced by Silica Nanoparticles

Liquid crystalline networks (LCNs) are a class of polymers, which are able to produce mechanical actuation in response to external stimuli. Recent creation of LCNs with exchangeable links (xLCNs) makes LCNs easy moldable. As the xLCNs need to be shaped at a high temperature, it is important to enhance their thermal and mechanical properties. In this paper, a series of xLCNs/SiO₂ composites containing 1%–7% SiO₂ nanoparitcles (SNP) were prepared and their thermal and mechanical properties were examined. The results show that xLCNs/SNP composites have lower liquid crystalline-isotropic phase transition temperature and higher decomposition temperature than pure LCN. The tensile strength and the elongation at break of xLCNs at high temperatures were also enhanced due to the addition of SNPs.     

Investigation of the binding and cleavage characteristics of N1 neuraminidases from avian,seasonal, and pandemic influenza viruses using saturation transfer difference nuclear magnetic resonance

Objectives

The main function of influenza neuraminidase (NA) involves enzymatic cleavage of sialic acid from the surface of host cells resulting in the release of the newly produced virions from infected cells, as well as aiding the movement of virions through sialylated mucus present in the respiratory tract. However, there has previously been little information on the binding affinity of different forms of sialylated glycan with NA. Our objectives were then to investigate both sialic acid binding and cleavage of neuraminidase at an atomic resolution level.

Design

Nuclear magnetic resonance (NMR) spectroscopy was used to investigate pH and temperature effects on binding and cleavage as well as to interrogate the selectivity of human-like or avian-like receptors for influenza neuraminidase N1 derived from a range of different influenza virus strains including human seasonal H1N1, H1N1pdm09 and avian H5N1.

Results

We demonstrated that an acidic pH and physiological temperature are required for efficient NA enzymatic activity; however a change in the pH had a minimum effect on the NA-sialic acid binding affinity. Our data comparing α-2,3- and α-2,6-sialyllactose indicated that the variation in neuraminidase activity on different ligands correlated with a change in binding affinity. Epitope mapping of the sialylglycans interacting with NAs from different viral origin showed different binding profiles suggesting that different binding conformations were adopted.

Conclusions

The data presented in this study demonstrated that physicochemical conditions (pH in particular) could affect the NA enzymatic activity with minor effect on ligand binding. NA cleavage specificity seemed to be associated with a difference in binding affinity to different ligands, suggesting a relationship between the two events. These findings have implications regarding the replication cycle of influenza infection in the host where different sialidase activities would influence penetration through the respiratory mucin barrier and the release of the newly generated virus from the infected cells.     

Observations on the epidemiology of gastrointestinal and liver cancers in the Asia–Pacific region

Gastric cancer (GC) has long been thought to be an Asian type of cancer that is broadly associated with poverty, whereas colorectal cancer (CRC) has been thought to be a Western type of cancer associated with affluence. The incidence of GC has declined dramatically in the West but has a very high incidence in East Asia. The age‐standardized incidence rates (ASR) have also declined. The decrease in the incidence of GC is associated with the decrease in the prevalence of Helicobacter pylori (H. pylori) infection worldwide. The discrepancy between a high H. pylori infection rate and a low GC incidence is seen chiefly among southern Asians of Indian origin and has been aptly termed the “Indian enigma”. CRC is a new emerging cancer in this region. Some of the highest CRC ASR have been reported from Asian countries, in many of which it has now surpassed that of GC. Liver cancer is also an important cancer in the Asia–Pacific region. The highest ASR worldwide is reported from the Asian countries of Mongolia, Korea and Japan. The predominant underlying etiology across the region has been hepatitis B virus infection, except in Japan, where hepatitis C is an important cause of hepatocellular carcinoma (HCC). With mass vaccination of hepatitis B at birth and improved public health measures in many countries, hepatitis B and C are set to decline with time. However, the exponential increase in obesity and consequent non‐alcoholic fatty liver disease portends a future epidemic of fatty liver‐related HCC.     

Effects of Cognitive-Behavioral Therapy on Improving Anxiety Symptoms,Behavioral Problems and Parenting Stress in Taiwanese Children with Anxiety Disorders and Their Mothers

The aims of this intervention study were to examine the effects of individual cognitive-behavioral therapy (CBT) based on the modified Coping Cat Program on improving anxiety symptoms and behavioral problems in Taiwanese children with anxiety disorders and parenting stress perceived by their mothers. A total of 24 children with anxiety disorders in the treatment group completed the 17-session individual CBT based on the modified Coping Cat Program, and 26 children in the control group received the treatment as usual intervention. The Taiwanese version of the MASC (MASC-T), the Child Behavior Checklist for Ages 6–18 (CBCL/6-18) and the Chinese version of the Parenting Stress Index (C-PSI) were applied to assess the severities of anxiety symptoms, behavioral problems and parenting stress, respectively. The effects of CBT on improving anxiety symptoms, behavioral problems and parenting stress were examined by using linear mixed-effect model with maximum likelihood estimation. The results indicated that the CBT significantly improved the severities of MASC-T Physical Symptoms and Social Anxiety subscales, CBCL/6-18 DSM-oriented Anxiety Problem subscale, and C-PSI Child domains Mood and Adaptability subscales. Individual CBT based on the modified Coping Cat Program can potentially improve anxiety symptoms in Taiwanese children with anxiety disorders and some child domains of parenting stress perceived by their mothers.