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Amyotrophic lateral sclerosis (ALS) is a progressively paralytic neurodegenerative disease that can be caused by mutations in Cu/Zn-superoxide dismutase 1 (SOD1). Transgenic mice that overexpress mutant SOD1 develop paralysis and accumulate aggregates of mutant protein in the brainstem and spinal cord. Bee venom (BV), which is also known as apitoxin, is extracted from honeybees and is commonly used in oriental medicine for the treatment of chronic rheumatoid arthritis and osteoarthritis. The purpose of the present study was to determine whether BV affects misfolded protein aggregates such as alpha-synuclein, which is a known pathological marker in Parkinson disease, and ubiquitin-proteasomal activity in hSOD1G93A mutant mice. BV was bilaterally administered into a 98-day-old hSOD1G93A animal model. We found that BV-treated hSOD1G93A transgenic mice showed reduced detergent-insoluble polymerization and phosphorylation of α-synuclein. Furthermore, phosphorylated or nitrated α-synuclein was significantly reduced in the spinal cords and brainstems of BV-treated hSOD1G93A mice and reduced proteasomal activity was revealed in the brainstems of BV-treated symptomatic hSOD1G93A. From these findings, we suggest that BV treatment attenuates the dysfunction of the ubiquitin-proteasomal system in a symptomatic hSOD1G93A ALS model and may help to slow motor neuron loss caused by misfolded protein aggregates in ALS models

Potassium chloride elicits enhancement of bilobalide and Ginkgolides production by Ginkgo biloba cell cultures

This study investigated the ability of potassium chloride (KCl) to elicit the production of bilobalide (BB), ginkgolide A (GA) and ginkgolide B (GB) by Ginkgo biloba cell suspension cultures. The salt stress by KCl treatments increased production of BB, GA and GB in both suspended cells and cultured medium. Especially, treatment of KCl 800 mM of highest concentration was stimulated emission into cultured medium BB, GA and GB compounds accumulated in cells. Although KCl 800 mM severely inhibited cells growth, the maximum content of GA and GB in cells was obtained in the treatment of KCl 800 mM, which was 1.9 and 4.0 times higher than the control. These results thus suggest that salt stress can afford enhanced production of secondary metabolites by plant cell cultures

Melittin restores proteasome function in an animal model of ALS

Amyotrophic lateral sclerosis (ALS) is a paralyzing disorder characterized by the progressive degeneration and death of motor neurons and occurs both as a sporadic and familial disease. Mutant SOD1 (mtSOD1) in motor neurons induces vulnerability to the disease through protein misfolding, mitochondrial dysfunction, oxidative damage, cytoskeletal abnormalities, defective axonal transport- and growth factor signaling, excitotoxicity, and neuro-inflammation

5-Fluoro­isophthalic acid

In the crystal structure of the title compound, C8H5FO4, the complete molecule is generated by crystallographic twofold symmetry with two C atoms and the F atom lying on the axis. The mol­ecule is almost planar with the carboxyl group twisted with respect to the mean plane of the benzene ring by a dihedral angle of 2.01 (1)°. In the crystal, inter­molecular O—H⋯O hydrogen bonds and C—H⋯F inter­actions connect the mol­ecules into a two-dimensional supra­molecular array

Selection of high berberine yielding phellodendron insulare nak. lines and the antimicrobial activity of their extracts

High berberine yielding Phellodendron insulare Nak. lines were selected by aggregate cloning method and the antimicrobial activity of their extracts was assessed. The berberine producing cork tree lines were selected by adopting a colorimetric method. In all 300 high berberine producing lines were selected with a colorimetric reagent containing 5M HCl and H2O2 and established from dissociated cell aggregates. The crude extracts from these lines showed antibacterial activities against tested Escherichia coli, Staphylococcus aureus, Salmonella typhimulium, and Listeria monocytogenes. The cork tree extracts were found to be inhibitory to these test organisms. Further the antimicrobial activity of plant extracts was on par with the berberine isolated from the extracts from native cork trees. These results have potential for developing alternative plant products as antimicrobial substances for application in agriculture and food industry

Associations between Organochlorine Pesticides and Vitamin D Deficiency in the U.S. Population

Background: Recently low dose organochlorine (OC) pesticides have been strongly linked to various chronic diseases including diabetes and cardiovascular diseases. Both field and animal studies have suggested a possibility that persistent lipophilic chemicals like OC pesticides can cause vitamin D deficiency, but there have been no human studies of exposure to any chemical as a possible cause of vitamin D deficiency. This study was performed to examine if serum concentrations of OC pesticides were associated with serum concentrations of 25-hydroxyvitamin D (25(OH)D) in the U.S. general population. Methodology/Principal Findings: Cross-sectional associations of serum OC pesticides with serum 25(OH)D were investigated in 1,275 subjects aged $20 in the National Health and Nutrition Examination Survey(NHANES), 2003–2004. We selected 7 OC pesticides detectable in$80 % of participants. Among the 7 OC pesticides, p,p9-DDT (b = 20.022, P,0.01), p,p9-DDE (b = 20.018, P = 0.04), and b-hexachlorocyclohexane (b = 20.022, P = 0.02) showed significant inverse associations with serum 25(OH)D levels. When study subjects were stratified by age, race, and the presence of various chronic diseases, p,p9-DDT showed consistent inverse associations in all subgroups, although stronger associations tended to be observed among subjects with old age, white race, or chronic diseases. Conclusion/Significance: The current study suggests that the background exposure to some OC pesticides leads to vitamin D deficiency in human. Considering the importance of vitamin D deficiency in the development of chronic diseases

Bee venom attenuates neuroinflammatory events and extends survival in amyotrophic lateral sclerosis models

<p>Abstract</p> <p>Background</p> <p>Amyotrophic lateral sclerosis (ALS) is a disease affecting the central nervous system that is either sporadic or familial origin and causing the death of motor neurons. One of the genetic factors contributing to the etiology of ALS is mutant SOD1 (mtSOD1), which induces vulnerability of motor neurons through protein misfolding, mitochondrial dysfunction, oxidative damage, cytoskeletal abnormalities, defective axonal transport, glutamate excitotoxicity, inadequate growth factor signaling, and neuroinflammation. Bee venom has been used in the practice of Oriental medicine and evidence from the literature indicates that BV plays an anti-inflammatory or anti-nociceptive role against inflammatory reactions associated with arthritis and other inflammatory diseases. The purpose of the present study was to determine whether bee venom suppresses motor neuron loss and microglial cell activation in hSOD1^G93Amutant mice.</p> <p>Methods</p> <p>Bee venom (BV) was bilaterally injected (subcutaneously) into a 14-week-old (98 day old) male hSOD1^G93Aanimal model at the Zusanli (ST36) acupoint, which is known to mediate an anti-inflammatory effect. For measurement of motor activity, rotarod test was performed and survival statistics were analyzed by Kaplan-Meier survival curves. The effects of BV treatment on anti-neuroinflammation of hSOD1^G93Amice were assessed via immunoreactions using Iba 1 as a microglia marker and TNF-α antibody. Activation of ERK, Akt, p38 MAP Kinase (MAPK), and caspase 3 proteins was evaluated by western blotting.</p> <p>Results</p> <p>BV-treated mutant hSOD1 transgenic mice showed a decrease in the expression levels of microglia marker and phospho-p38 MAPK in the spinal cord and brainstem. Interestingly, treatment of BV in symptomatic ALS animals improved motor activity and the median survival of the BV-treated group (139 ± 3.5 days) was 18% greater than control group (117 ± 3.1 days). Furthermore, we found that BV suppressed caspase-3 activity and blocked the defects of mitochondrial structure and cristae morphology in the lumbar spinal cord of hSOD1^G93Amice at the symptomatic stage.</p> <p>Conclusion</p> <p>From these findings, our research suggests BV could be a potential therapeutic agent for anti-neuroinflammatory effects in an animal model of ALS.</p

A PDEM-COM framework for uncertainty quantification of backward issues involving both aleatory and epistemic uncertainties

Uncertainties that exist in nature or due to lack of knowledge have been widely recognized by researchers and engineering practitioners throughout engineering design and analysis for decades. Though great efforts have been devoted to the issues of uncertainty quantification (UQ) in various aspects, the methodologies on the quantification of aleatory uncertainty and epistemic uncertainty are usually logically inconsistent. For instance, the aleatory uncertainty is usually quantified in the framework of probability theory, whereas the epistemic uncertainty is quantified mostly by non-probabilistic methods. In the present paper, a probabilistically consistent framework for the quantification of both aleatory and epistemic uncertainty by synthesizing the probability density evolution method (PDEM) and the change of probability measure (COM) is outlined. The framework is then applied to the backward issues of uncertainty quantification. In particular, the uncertainty model updating issue is discussed in this paper. A numerical example is presented, and the results indicate the flexibility and efficiency of the proposed PDEM-COM framework

Effects of Bee Venom on Glutamate-Induced Toxicity in Neuronal and Glial Cells

Bee venom (BV), which is extracted from honeybees, is used in traditional Korean medical therapy. Several groups have demonstrated the anti-inflammatory effects of BV in osteoarthritis both in vivo and in vitro. Glutamate is the predominant excitatory neurotransmitter in the central nervous system (CNS). Changes in glutamate release and uptake due to alterations in the activity of glutamate transporters have been reported in many neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. To assess if BV can prevent glutamate-mediated neurotoxicity, we examined cell viability and signal transduction in glutamate-treated neuronal and microglial cells in the presence and absence of BV. We induced glutamatergic toxicity in neuronal cells and microglial cells and found that BV protected against cell death. Furthermore, BV significantly inhibited the cellular toxicity of glutamate, and pretreatment with BV altered MAP kinase activation (e.g., JNK, ERK, and p38) following exposure to glutamate. These findings suggest that treatment with BV may be helpful in reducing glutamatergic cell toxicity in neurodegenerative diseases