bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of AOB, a fermented‐grain food supplement, on oxidative stress in type 2 diabetic rats
Authors: Minamiyama Yukiko , Takemura Shigekazu , Tsukioka Takuma , Shinkawa Hiroji , Kobayashi Fumiko , Nishikawa Yuriko , Kodai Shintaro , Mizuguchi Shinjiro , Suehiro Shigefumi , Okada Shigeru
Published: December 2008

Reactive oxygen species (ROS) play an important role in the pathogenesis of diabetic complications. Antioxidant Biofactor (AOB) is a mixture of commercially available fermented grain foods and has strong antioxidant activity. This study investigated the effect of AOB supplementation of standard rat food on markers of oxidative stress and inflammation in Otsuka Long‐Evans Tokushima Fatty (OLETF) rats with type 2 diabetes. Blood glucose, hemoglobin A1c, plasma free fatty acid, triacylglycerol and plasminogen activator inhibitor‐1 (PAI‐1) were significantly higher in OLETF rats than in non‐diabetic control Long‐Evans Tokushima Otsuka (LETO) rats at 29 weeks. AOB (6.5% of diet) was given to rats during 29–33 weeks of diabetic phase in OLETF rats.

OLETF rats with AOB supplementation showed decreased blood glucose, hemoglobin A1c, triacylgycerol, low density lipoprotein, cholesterol and PAI‐1. Mitochondrial ROS production was significantly increased in heart, aorta, liver and renal artery of OLETF rats. Uncoupling protein 2 (UCP2) is known to regulate ROS production. We found aortic UCP2 protein expression increased in OLETF rats, and AOB returned UCP2 expression to normal.

Aortic endothelial NO synthase (eNOS) was also increased in OLETF rats more than in LETO rats at 33 weeks. In contrast, phosphorylated vasodilator‐stimulated phosphoprotein, an index of the NO‐cGMP pathway, was significantly diminished. AOB increased eNOS proteins in LETO and OLETF rats. In conclusion, AOB significantly improved the NO‐cGMP pathway via normalizing ROS generation in OLETF rats. The data suggest that dietary supplementation with AOB contributes to nutritional strategies for the prevention and treatment of type 2 diabetes mellitus.
Water extract ofCordyceps sinensis(WECS) inhibits the RANKL‐induced osteoclast differentiation
Authors: Mizuha Yoko , Yamamoto Hironori , Sato Tadatoshi , Tsuji Mitsuyoshi , Masuda Masashi , Uchida Masayuki , Sakai Kentaro , Taketani Yutaka , Yasutomo Koji , Sasaki Hajime , Takeda Eiji
Published: December 2008

It has been reported thatCordyceps sinensis, a traditional Chinese medicine, has various pharmacological effects. The aim of this study was to clarify the effect of water extract ofCordyceps sinensis(WECS) on osteoclast differentiationin vitro. In mouse bone marrow cells and monocyte/macrophage cell line RAW264.7, WECS dose‐dependently inhibited the receptor activator of nuclear factor kappa B (NF‐κB) ligand (RANKL)‐induced osteoclast differentiation by tartrate‐resistant acid phosphatase (TRAP) staining. In fact, cytotoxic effect was not observed in the RAW264.7 cells treated with WECS. Moreover, the mRNA expression of osteoclast related genes (calcitonin receptor, cathepsin K, matrix metalloprotease 9 and nuclear factor of activated T cells c1) was also inhibited by WECS. Investigation of inhibitory mechanism by using electrophoretic mobility shift assay (EMSA) and Western blot analysis revealed that WECS inhibited the activation of NF‐κB through the prevention of IκBα phosphorylation. In conclusion, the present results demonstrate for the first time that WECS is a potent inhibitor of the RANKL‐induced osteoclast differentiation through a mechanism involving the NF‐κB pathway.
Local and systemic impacts of pleural oxygen exposure in thoracotomy
Authors: Tsukioka Takuma , Takemura Shigekazu , Minamiyama Yukiko , Nishiyama Noritoshi , Mizuguchi Shinjiro , Okada Shigeru , Suehiro Shigefumi
Published: December 2008

The pleural cavity is normally in a state of negative pressure and low oxygen tension. It is exposed to the atmosphere during thoracic surgery. However, no reports of pathophysiological investigation of the effects of pleural oxygen exposure involved in thoracotomy are available. In this study, the effects of pleural oxygen exposure on systemic and pleural inflammation were investigated. Male Wistar rats (9 weeks old) were placed on mechanical ventilation and underwent thoracotomy with lipopolysaccharide (LPS) administration, which simulates latent inflammatory condition. The pleural cavity was exposed to nitrogen (N2 thoracotomy group), air (20% oxygen, air thoracotomy group), or 100% oxygen (O2 thoracotomy group) under mechanical ventilation for 2 h. Animals were sacrificed 2 h or 8 h after LPS administration, and inflammatory indices (plasma tumor necrosis factor‐α and interleukin‐6, histology) were examined. For examination of inflammatory mediators, pleural effusion was added to cultured RAW264 cells, a murine macrophage cell line, and tumor necrosis factor‐α levels in supernatant were measured. The capacity of pleural superoxide generation was investigated without LPS administration. Results showed increases in plasma interleukin‐6 concentration and lung injury in the air and O2 thoracotomy groups. Pleural oxygen exposure stimulated pleural superoxide generation, and increased pleural 4‐hydroxy–2‐nonenal and lung lipid peroxide concentrations. Tumor necrosis factor‐α levels in cell culture supernatants were increased by the addition of pleural effusion from the air and O2 thoracotomy groups. In conclusion, pleural oxygen exposure induced pleural oxidative injury and aggravated latent systemic inflammatory response.
Coenzyme Q10 effects on manganese superoxide dismutase and glutathione peroxidase in the hairless mouse skin induced by ultraviolet B irradiation
Authors: Kim Dong‐Woo , Hwang In Koo , Kim Dae Won , Yoo Ki‐Yeon , Won Chung‐Kil , Moon Won‐Kook , Won Moo‐Ho
Published: December 2008

Coenzyme Q10 (CoQ10 ) is a naturally occurring antioxidant and a prominent component of mitochondrial electron transport chain. In the present study, we investigated the effect of CoQ10 nanoparticle against photoaging using immunohistochemistry and Western blot analysis in the hairless mouse skin induced by ultraviolet B (UVB) irradiation (300 mJ/cm2, 3 min/day for 21 days). In the UVB‐irradiated distilled water (DW)‐treated group, manganese superoxide dismutase (SOD2) and glutathione peroxidase (GPx) immunoreactivity and their protein levels in the skin were significantly lower than those in the control group. However, SOD2 and GPx immunoreactivity and their protein levels in the skin of the UVB‐irradiated CoQ10 treated group were higher than those in the UVB‐irradiated DW‐treated group. GPx activity in the skin in the UVB‐irradiated DW‐treated group significantly decreased compared to that in the control group; whereas GPx activity in the UVB‐irradiated CoQ10 ‐treated group was similar to that in the control group. These results suggest that CoQ10 strongly inhibits oxidative stress in the skin induced by UVB via increasing SOD2 and GPx.
Enhanced pro‐apoptotic and anti‐adipogenic effects of genistein plus guggulsterone in 3T3‐L1 adipocytes
Authors: Yang Jeong‐Yeh , Della‐Fera Mary Anne , Rayalam Srujana , Ambati Suresh , Baile Clifton A.
Published: December 2008

Genistein (G), an isoflavone, and guggulsterone (GS), the active substance in guggulipid, have been reported to possess therapeutic effects for obesity. In the present study, we investigated the effects of combinations of G plus GS on apoptosis and adipogenesis in 3T3‐L1 cells. In mature adipocytes, G and GS individually caused apoptosis, but combination of G plus GS significantly increased apoptosis, more than either compound alone. Furthermore, G plus GS caused a greater increase in procaspase‐3 cleavage, Bax expression, cytochrome c release, and proteolytic cleavage of PARP than either compound alone. In maturing preadipocytes G and GS each suppressed lipid accumulation, but the combination potentiated the inhibition of lipid accumulation. These results suggest that combination of genistein and guggulsterone may exert anti‐obesity effects by inhibiting adipogenesis and inducing apoptosis in adipocytes.
Effects of antioxidant stobadine on protein carbonylation, advanced oxidation protein products and reductive capacity of liver in streptozotocin‐diabetic rats: Role of oxidative/nitrosative stress
Authors: Cumaoǧlu Ahmet , Cevik ÇEmal , Rackova Lucia , Ari Nuray , Karasu ÇImen
Published: December 2008

Background: Increased oxidative/nitrosative stress is important in the pathogenesis of diabetic complications, and the protective effects of antioxidants are a topic of intense research. The purpose of this study was to investigate whether a pyridoindole antioxidant stobadine (STB) have a protective effect on tissue oxidative protein damage represented by the parameters such as protein carbonylation (PC), protein thiol (P‐SH), total thiol (T‐SH) and non‐protein thiol (Np‐SH), nitrotyrosine (3‐NT), and advanced oxidation protein products (AOPP) in streptozotocin‐diabetic rats.

Methods: Diabetes was induced in male Wistar rats by intraperitonal injection of streptozotocin (55 mg/kg). Some of the non‐diabetic (control) and diabetic rats treated with STB (24.7 mg/kg/day) during 16 weeks, and the effects on blood glucose, PC, AOPP, 3‐NT, P‐SH, T‐SH and Np‐SH were studied. Biomarkers were assayed by enzyme‐linked immunosorbent assay (ELISA) or by colorimetric methods.

Results: Administration of stobadine to diabetic animals lowered elevated blood glucose levels by ∼16% relative to untreated diabetic rats. Although stobadine decreased blood glucose, poor glycemic control was maintained in stobadine treated diabetic rats during the treatment period. Biochemical analyses of liver proteins showed significant diminution of sulfhydryl groups, P‐SH, T‐SH, Np‐SH, and elevation of carbonyl groups in diabetic animals in comparison to healthy controls. As a biomarker of nitrosative stress, 3‐NT levels did not significantly change by diabetes induction or by stobadine treatment when compared to control animals. However, the treatment with stobadine resulted in a significant decrease in PC, AOPP levels and normalized P‐SH, T‐SH, Np‐SH groups in liver of diabetic animals.
Citrus nobiletin suppresses bone loss in ovariectomized ddY mice and collagen‐induced arthritis in DBA/1J mice: Possible involvement of receptor activator of NF‐kappaB ligand (RANKL)‐induced osteoclastogenesis regulation
Authors: Murakami Akira , Song Meiyu , Katsumata Shin‐Ichi , Uehara Mariko , Suzuki Kazuharu , Ohigashi Hajime
Published: December 2008

Bone resorption is known to accelerate during the onset of several disorders, including osteoporosis (OP) and rheumatoid arthritis (RA). Some epidemiological surveys have suggested that a high intake of vegetables and fruits has an inverse relation to such disease incidence, though the number of active constituents elucidated thus far is limited. In the present study, we examined the efficacy of various food phytochemicals using two animal models. First, female ddY mice were ovariectomized (OVX) or sham‐operated (sham), after which five different compounds (phenethyl isothiocyanate, zerumbone, auraptene, 1'‐acetoxychavicol acetate, and nobiletin) were administered separately to OVX mice with a mini‐osmotic pump at doses of 0.25 or 0.5 mg/day for 4 weeks, with 17β‐estradiol (E2, 0.03 μg/day) used as a positive control. Nobiletin, in contrast to the other tested phytochemicals, significantly (P < 0.05) suppressed the reduction of whole bone mineral density by 61%, which was comparable to or higher than the efficacy of E2 . Next, nobiletin given as an i.p. administration at 20 mg/kg of body weight, but not 2 mg/kg, to male DBA/1J mice every 2 days for 12 days led to a marked decrease in type II collagen‐induced arthritis by 45% (P < 0.05). Furthermore, the flavonoid (4–50 μM) attenuated receptor activator of nuclear factor kappaB ligand (RANKL)‐induced osteoclastogenesis of RAW264.7 cells, as detected by tartarate‐resistant acid phosphatase activity and microscopic observations. Of note, nobiletin also suppressed RANKL‐activated extracellular signal‐regulated kinase1/2, c‐Jun N‐terminal kinase1/2, and p38 mitogen‐activated protein kinase activities, and thereby regulated the promoter activation of nuclear factor kappaB (NFκB) and activator protein‐1, key transcription factors for differentiation. Together, our results suggest that nobiletin is a promising phytochemical for the prevention or treatment of osteoclastogenesis‐related disorders, including OP and RA, with reasonable action mechanisms.
Application of poly ethylene glycol hydrogel to overcome latex urinary catheter related problems
Authors: Sankar Sriram , Rajalakshmi T.
Published: December 2008

Urinary catherization is a routine procedure in an intensive care unit (ICU) for monitoring the urine output of critically ill patients. The catheters which are most often used to help with urinary incontinence and retention also face problems like blockage, leakage and infection. These problems are due to proteins that adhere to the catheter surface and quickly build up on each other forming a protein layer. As the layers build up they can crystallize, providing the major source of blockage and leakage. Current strategies to avoid these problems include coating a catheter with silver alloy to reduce bacteria on the catheter surface. However, silver alloy coatings can lead to increased silver resistance for bacteria. Since silver is already used as an antibacterial agent in many places in a hospital, it is even more possible that resistance can develop. An alternative solution is presented involving coating latex, a common urinary catheter material with a micro layer (5‐100 microns) of polyethylene glycol. This hydrogel is applied using an interfacial photopolymerizatoin process with ethyl eosin as the photoinitiator. A 25 ppm concentration of ethyl eosin provided the strongest gel to surface adhesion and significantly lowered protein adhesion when compared to an uncoated latex substrate.
Immobilization of derivatized dextran nanoparticles on konjac glucomannan/chitosan film as a novel wound dressing
Authors: Zhang Hui , Gu Chun‐Hu , Wu Hong , Fan Li , Li Fei , Yang Fan , Yang Qian
Published: December 2008

The aim of this study was to prepare konjac glucomannan (KGM)/chitosan (CS) film containing glycidyl methacrylate derivatized dextran (dex‐GMA)/acrylic acid(AAc) nanoparticles loaded with antibacterial agent. In this study, An optimized procedure chosen from three methods was used to prepare Erythromycin (EM)‐loaded poly(dex‐GMA/AAc) nanoparticles and obtained nanoparticles ranged from 50–200 nm. Film was found to have equilibrium water content (EWC) 99.3% which could prevent exudates on wound bed from accumulating and also have excellent water adsorption 2362.3 ± 55.2%; the water vapor transmission rate (WVTR) was 2335 ± 36 gm−2 day−1 and evaporative water loss from the film (EWL) was approximately 10% after 1 h and within 6 h it increased to 90%. Drug release of film containing nanoparticles or absent was determined, within 22 h accumulative release was 40.3%, 72.5% respectively. In conclusion, KGM/CS film containing nanoparticles could not only maintain a moist environment over wound bed in moderate to heavily exuding wound but also provide a continuous and sustained release of the antibacterial agent on the wound surface, which could be potential wound dressing.
Role of endogenous zinc in bones of newborn rats
Authors: Drzazga Z. , Michalik K. , Maciejewska K. , Trzeciak H. , Kaszuba M.
Published: December 2008

Concentration of abundant elements e.g. calcium as well as of elements present in trace amount e.g. zinc in mandibles of 7, 14 an 28 day old newborn rats were determined by X‐ray fluorescence analysis.

The measurements were carried out by using a measurement system containing X‐ray tube ECLIPSE‐III and X‐ray and gamma ray detector XR‐100T‐CdTe (Amptek Inc.).

Concentration of calcium and zinc depended on the region of interest on the rat's mandible due to mineralization degree conditioned by its function. Increasing age produced a remarkable increase in Ca content in contrast to Zn content in the bone tissue obtained from 7, 14 and 28 day old newborn rats. The calculated Zn/Ca concentration ratio was the biggest for 7 day old newborns and successively decreased with age indicating the important role of zinc at the beginning of bone ontogenesis.
Amplified protein sensing using deep purple fluorophores on homogeneous Au substrates
Authors: Xie Fang , Goldys Ewa , Baker Mark
Published: December 2008

We report here the first observation of appreciable enhancement of fluorescence induced by large Au colloids. Au monolayers with Au colloids of 40 nm, 59 nm, and 81 nm in radii, were formed on silane modified glass surfaces, respectively. The nanoparticle densities were varied by varying the deposition times and documented by scanning electron microscopy. Two types of samples were prepared, with large inter‐particle distance and hence little or no inter‐particle coupling and small inter‐particle distance with inter‐particle coupling. The fluorescence enhancement was examined by using a self assembled monolayer of the fluorophore‐protein conjugate with Deep Purple as a fluorophore and Bovine Serum Albumin as protein (DP‐BSA). The data show the over 15 fold enhancement under optimized conditions and reveal strong variations with both inter‐particle distance and particle size. Nanostructures of appropriate size with optimized inter‐particle distance thus prepared can produce promising substrates for decent fluorescence enhancement. We demonstrated that the Au colloid monolayers on glass surfaces are promising substrates for fluorescence enhancement with outstanding macroscopic homogeneity. This important feature will pave the way for the application of our substrates in biotechnology and life sciences such as imaging and sensing of biomolecules in proteomics.
Monte Carlo simulation of NIR diffuse reflectance in the normal and diseased human breast tissues
Authors: Prince Shanthi , Malarvizhi S.
Published: December 2008

The spectral reflectance measurements in tissue reveal physiological meaning. Normally, functional changes like, increase in total hemoglobin concentration, decrease in oxygen saturation, etc., are observed when there is an abnormality creeping in the normal tissue. These functional changes can act together to reveal disease by non‐invasive near‐infrared (NIR) spectroscopy, as it influence its optical properties.

In the present study, a simple two dimensional, four layer model of breast is proposed. The four layers are (i) skin (ii) adipose layer (iii) glandular tissue and (iv) muscle. Each layer is modeled with appropriate biological chromophores like hemoglobin, water, lipid and melanin. From the literature, the concentrations and molar extinction coefficients of the chromophores in various layers of the model are obtained. These values are used to calculate the wavelength dependent absorption characteristics of a particular layer.

Monte Carlo simulation of diffuse reflectance (percentage of back reflected photons after multiple scattering with the broad variety of angles) are simulated for the modeled breast tissue with and without diseased condition. Near‐infrared wavelengths are chosen, as the depth of penetration in tissue is more compared to UV and visible region. Simulations are carried out on the modeled breast tissue for different races (skin colors) at different NIR wavelengths. Results show significant changes in diffuse reflectance and relative absorbance for normal and diseased breast tissues for differently pigmented model. This model can be used to study the photo dynamical therapy, drug delivery and prognosis of cancer.
A novel high resolution micro‐radiotherapy system for small animal irradiation for cancer research
Authors: Wang Sigen , Liu Zhijun , Sultana Shabana , Schreiber Eric , Zhou Otto , Chang Sha
Published: December 2008

Micro‐radiotherapy (micro‐RT) system is specially designed for small animal (cancer cell) irradiation for basic and translational cancer research. We use carbon nanotube (CNT) field emission technology to develop a novel micro‐RT system for image‐guided high precision irradiation that is similar to the state of the art radiotherapy which our cancer patients receive today at mouse scale. Through the field emission control of its individually addressable x‐ray pixel beams the micro‐RT system electronically shapes the radiation field and forms intensity modulation pattern. In this paper, we present the development of a carbon nanotube field emission cathode array chip — a key component for our novel micro‐RT system. The prototype micro‐RT CNT field emission cathode array chip has 5×5 individually addressable cathode pixels that are 1 mm in diameter and 2 mm in pitch. An individual CNT cathode pixel is predicted to generate a dose rate in the order of 100 cGy/min at the center of the irradiated mouse based on our Monte Carlo simulation. The temporal and spatial resolutions of the micro‐RT system are expected to be ∼ms level and <2 mm respectively.
Glucose sensors made of novel carbon nanotube‐gold nanoparticle composites
Authors: Cai Dong , Yu Ying , Lan Yucheng , Dufort Fay J. , Xiong Guangyong , Paudel Trilochan , Ren Zhifeng , Wagner Dean J. , Chiles Thomas C.
Published: December 2008

Carbon nanotube and metal particle composites have been exploited to fabricate high performance electrochemical devices. However, the physical and chemical procedures to synthesize the composites are labor intensive and inefficient. Our study reveals an one‐step wet chemistry method to accomplish fast and controllable production of gold nanoparticle (AuNP) and carbon naotube (CNT) composites. Such a process is sensitive to the surface charge. Especially, when functionalized with carboxyl groups, the CNTs carried negative charges and showed low level association with negatively charged AuNPs. Thermal treatment was employed to decompose the carboxyl groups and render each CNT a charge‐free surface thereby achieving a high level AuNP‐CNT association. The fabricated glucose sensors demonstrated dependence of their sensitivities to the amount of AuNPs on the CNTs. The enhancement of sensitivity can be attributed to an accelerated electron transfer rate from glucose oxidase Gox to the electrode. The Michaelis‐Menten kinetics also indicated improved performance in the glucose sensor made of AuNP‐CNTs. Therefore, our research revealed a novel approach to produce metallic nanoparticle and CNT composite for fabricating high performance electrochemical sensors.
Study on the biochemical characterization of herbicide detoxification enzyme, glutathione S ‐transferase
Authors: Cho Hyun‐Young , Kong Kwang‐Hoon
Published: December 2008

To gain further insight into herbicide detoxification, we studied the herbicide activity and specificity toward glutathione S‐transferases from human and rice. In this study, the genes of the plant specific phi and tau class GST enzymes from Oryza sativa (OsGST) and human pi class GST enzyme (hGSTP1‐1) were cloned and expressed in Escherichia coli with the pET and pKK vector systems, respectively. The gene products were purified to homogeneity by GSH Sepharose affinity column chromatography. The herbicide specificity of the enzymes was investigated by enzyme‐catalyzed conjugation of GSH with chloroacetanilide, diphenylether and chloro‐s‐triazine herbicides. The hGSTP1‐1 showed very high specific activity toward atrazine. On the other hand, the phi class OsGST enzymes showed high specific activity toward chloroacetanilide herbicides, acetochlor, alachlor and metolachlor. The tau class GST enzymes displayed remarkable activity toward the diphenylether herbicide, fluorodifen. From these results, we conclude that the phi and the tau class GST enzymes show herbicide specificities and also they play an important role in the detoxification reaction of plant toward herbicides.
Suppression of influenza A virus nuclear antigen production and neuraminidase activity by a nutrient mixture containing ascorbic acid, green tea extract and amino acids
Authors: Jariwalla R. J. , Roomi M. W. , Gangapurkar B. , Kalinovsky T. , Niedzwiecki A. , Rath M.
Published: December 2008

influenza, one of the oldeist and most common infections, poses a serious health problem causing significant morbidity and mortality, and imposing substantial economic costs. The efficacy of current drugs is limited and improved therapies are needed. A unique nutrient mixture (NM), containing ascorbic acid, green tea extract, lysine, proline, N‐acetyl cysteine, selenium among other micronutrients, has been shown to exert anti‐carcinogenic and anti‐atherogenic activity both in vitro and in vivo. Many of the constituents of NM have been shown to have an inhibitory effect on replication of influenza virus and HIV. This prompted us to study the effect of NM on influenza A virus multiplication in infected cells and neuraminidase activity (NA) in virus particles. Addition of NM to Vero or MDCK cells post infection resulted in dose‐dependent inhibition of viral nucleoprotein (NP) production in infected cells. NM‐mediated inhibition of viral NP was selective and not due to cytotoxicity towards host cells. This antiviral effect was enhanced by pretreatment of virus with the nutrient mixture. Individual components of NM, namely ascorbic acid and green tea extract, also blocked viral NP production, conferring enhanced inhibition when tested in combination. Incubation of cell‐free virus with NM resulted in dose‐dependent inhibition of associated NA enzyme activity. In conclusion, the nutrient mixture exerts an antiviral effect against influenza A virus by lowering viral protein production in infected cells and diminishing viral enzymatic activity in cell‐free particles.
Antidiabetic potential of Citrus sinensis and Punica granatum peel extracts in alloxan treated male mice
Authors: Parmar Hamendra Singh , Kar Anand
Published: December 2008

An investigation on the effects of four different concentrations of peel extract from Citrus sinensis (CS) or Punica granatum (PG) in male mice revealed the maximum glucose lowering and antiperoxidative activities at 25 mg/kg of CS and 200 mg/kg of PG. In a separate experiment their potential was evaluated with respect to the regulation of alloxan induced diabetes mellitus. While a single dose of alloxan (120 mg/kg) increased the serum levels of glucose and α‐amylase activity, rate of water consumption and lipid peroxidation (LPO) in hepatic, cardiac and renal tissues with a parallel decrease in serum insulin level, administration of 25 mg/kg of CS or 200 mg/kg of PG was found to normalize all the adverse changes induced by alloxan, revealing the antidiabetic and anti peroxidative potential of test fruit peel extracts. Subsequent phytochemical analysis indicated that the high content of total polyphenols in the test peels might be related to the antidiabetic and antiperoxidative effects of the test peels.
Mulberry leaves protect rat tissues from immobilization stress‐induced inflammation
Authors: Lee Chooi Yeng , Cheng Hwee Ming , Sim Si Mui
Published: December 2008

The ability of the antioxidants in the mulberry leaves to protect Sprague‐Dawley rats from injuries caused by immobilization stress was studied as an indicator of the tissue bioavailability of antioxidants. Nitrite level, lipid peroxidation and total antioxidant activity (TAA) in the plasma and tissues were measured. There were hypertrophy of the adrenal glands and kidneys, significant increased levels of nitrite in the plasma and adrenal glands, elevated thiobarbituric acid reactive substances (TBARS) in the plasma, kidneys and spleen, and a reduction of TAA in the plasma, liver, adrenal glands, kidneys and spleen of the immobilized rats. Antioxidants in the mulberry leaf extract suppressed the increase of nitrite and TBARS. Adrenal glands appeared to be the target organ of the antioxidants in the leaf extract. The low dose mulberry antioxidants were more effective than pure rutin (4 mg/day) to protect the cells against inflammation and peroxidation induced by stress.
Antioxidative and cytoprotective effects of Artemisia capillaris fractions
Authors: Hong Jung‐Hee , Lee Ji‐Won , Park Jung‐Hyun , Lee In‐Seon
Published: December 2008

The antioxidant effects of Artemisia capillaris fractions against reactive oxygen species (ROS) were evaluated by measuring scavenging activities against 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) radical, superoxide (O ), hydroxyl (HO·) and 2 nitric oxide (NO·) radical. Among five solvent fractions, ethyl acetate fraction showed the highest total polyphenol and total flavonoid contents as 648.75 and 89.09 μg/mg, respectively. Also, the ethyl acetate fraction showed the highest scavenging activity; the 50% inhibitory concentration (IC50, μg/mg) value for DPPH, O, HO· and NO· radical scavenging were 4.76, 31.54, 69.34 and 74.63, respectively. Additionally, the highest inhibition of rat liver microsomal lipid peroxidation was observed by ethyl acetate fraction. Except for free radical‐mediated protein damage, ethyl acetate fraction showed the highest scavenging activity. The effect of Artemisia capillaris fractions on cell viability and DNA damage induced by H2O2 in Raw 264.7 cell were also evaluated by MTT and comet assay, respectively. The protective effect of ethyl acetate fraction, as indicated by cell viability increasing 71% and DNA breakage decreasing 51% as compared with H2O2 ‐treated positive control. These results suggest that ethyl acetate fraction possess significant ROS scavenging and protective effect against oxidative DNA damage.
Oxidation of glutathione and superoxide generation by inorganic and organic selenium compounds
Authors: Chen Jau‐Jiin , Boylan L. Mallory , Wu Chih‐Kang , Spallholz Julian E.
Published: December 2008

The carcinostatic activities of selenium (Se) compounds have been shown to be composition and concentration dependent. Several studies have indicated that the ratios between glutathione (GSH) and Se may play an important role in Se catalysis and toxicity. The present study examined the catalytic effect of three selenium compounds on GSH oxidation using lucigenin‐dependent chemiluminescence (CL) as an indirect measure of superoxide generation. Various GSH:Se ratios were assayed for the glutathione oxidase activity of selenite, selenocystamine and diselenodipropionic acid. CL emitted from the reaction of selenite with GSH increased more rapidly and was greater than those from the diselenides, but the diselenide CL reactions were sustainable. Both selenite‐ and diselenide‐induced CL were markedly suppressed by superoxide dismutase (SOD). Iodoacetic acid (IAc) effectively inhibited CL generated from selenite‐, selenocystamine‐ and diselenodipropionic acidcatalyzed GSH oxidation. These results suggest that GSH oxidation catalyzed by selenite, and the diselenides selenocystamine and diselenodipropionic acid, generated the superoxide radical in which the CL was inhibited by SOD. Furthermore, CL inhibition by IAc suggests that the catalytic species producing superoxide were the GSSe− or RSe− anion. This redox chemistry may be responsible for selenite and organoselenium toxicity and apoptosis, making possible the design and synthesis of organoselenium‐containing pharmaceuticals.
Pregnenolone and dexamethasone, modulators of cytochrome P450‐3A, not increase but reduce urinary α‐CEHC excretion in rats
Authors: Li Yi‐Jen , Shaw Huey‐Mei
Published: December 2008

In this study, the CYP3A inducer pregnenolone‐16α‐carbonitrile (PCN) and the CYP3A inhibitor ketoconazole (KCZ) were used to investigate whether the metabolism of α‐tocopherol to its metabolite, α‐carboxyethyl hydroxychroman (α‐CEHC), is CYP3A‐dependent in rats. In experiment 1, two groups of Wistar rats were fed for 3 wk with either a basal diet (containing 50 ppm of α‐tocopherol) or the same diet containing 10‐fold more α‐tocopherol. In the last 3 days, each group was divided into 2 subgroups which were given a single i.p. injection of either PCN at 75 mg/kg/d (P50 & P500 groups) or DMSO (D50 & D500 groups). The liver TBARS concentration was highest in the P50 group. Two‐way ANOVA analysis showed that α‐tocopherol levels in the plasma and liver were both significantly decreased by PCN (p < 0.0001), as were α‐CEHC levels in the urine (p = 0.0004). In experiment 2, α‐tocopherol levels in the liver were increased and α‐CEHC excretion in the urine decreased in the Wistar rats fed with KCZ containing diet. In experiment 3, Wistar rats administered with dexamethasone (DEX) significantly decreased α‐tocopherol levels in the plasma and liver and α‐CEHC levels in the urine. These data showed CYP3A is not a major contributor of the metabolism of α‐tocopherol to α‐CEHC. Nevertheless, vitamin E status was markedly reduced by CYP3A inducers due to increased lipid peroxidation and this would increase the consumption of α‐tocopherol in the liver.
Survival rate of preantral follicles derived from vitrified neonate mouse ovarian tissue by cryotop and conventional methods
Authors: Eimani H. , Mamzoji S. S. , Soleimani M. M. , Abnosi M. H. , Valojerdi M. Rezazadeh , Yazdi P. Eftekhari , Shahverdi A. , Guorabi H.
Published: December 2008

The aim of this study was to investigate the growth and survival rate of preantral follicles isolated from vitrified ovarian tissue by Cryotop and conventional methods. The ovaries of 14‐day‐old mice were separated and divided into four groups as following: Cryotop group, vitrified by Cryotop; CV (Conventional; CV) group, vitrified by conventional straw; toxicity test group and control group. After warming the vitrified ovaries, isolated preantral follicles from four groups were cultured for 4 days to compare survival rate and follicular growth between above‐mentioned groups. Survival rate (97.3%) in toxicity test group alike the control group (98.7%) were significantly higher (P < 0.05) than the Cryotop (92.7%) and CV (47.7%) groups. Increase in follicle diameters after 4 days in Cryotop and CV groups was significantly lower (P < 0.05) than the control and toxicity test groups, but growth and survival rate of follicles in Cryotop group was significantly higher (P < 0.05) than the CV group. These results demonstrated that ovarian tissue vitrification by Cryotop highly preserves the viability rate of preantral follicles.
Serum selenium concentration in healthy children living in Tehran
Authors: Safaralizadeh Reza , Sirjani Mahshid , Pourpak Zahra , Kardar Gholamali , Teimourian Shahram , Shams Sedigheh , Namdar Zahra , Kazemnejad Anoushiravan , Moin Mostafa
Published: December 2008

Introduction: Selenium is one of the essential trace elements which is more notifed in children in recent years. Reliable age‐specifc reference values for selenium in children in Iran are not clear and are important for the identifcation of selenium defciency and some other researches that is the aim of this study.

Methods: Serum samples of 216 healthy children were analyzed by using hydride generation and flame atomic absorption spectroscopy to measured selenium level.

Results: The mean and standard deviation of serum selenium level in children 0–16 years old (mean: 39.83 months) was 72.14 ± 16.80 μg/l. There was signifcant difference in serum selenium concentration between two sexes which was 76.78 ± 15.24 μg/l and 69.56 ± 17.09 μg/l in girls and boys respectively (P value = 0.002 ). There was also a positive correlation between higher selenium serum concentration and age in both sexes.

Conclusion: Essential trace element's normal ranges are fundamental data which could use in many studies. Serum selenium concentration in healthy Iranian children that found in this study is very close to serum concentration of European children. Our fndings may reveal nutritional culture's similarity.
Gene expression in arcuate nucleus‐median eminence of rats treated with leptin or ciliary neurotrophic factor
Authors: Ambati Suresh , Duan Jiuhua , Duff Emily , Choi Yang‐Ho , Hartzell Diane L. , Della‐Fera Mary Anne , Baile Clifton A.
Published: December 2008

Ciliary neurotrophic factor (CNTF) and leptin are cytokine‐like hormones and act on their corresponding receptors in the hypothalamic arcuate nucleus (ARC). The present study was designed to assess effects of intracerebroventricular (ICV) injection of leptin and CNTF on gene expression in micropunched hypothalamic arcuate nucleus‐median eminence (ARCME) complex samples from rats. Male Sprague Dawley rats were implanted with lateral cerebroventricular cannulas for administration of control, 10 μg/d leptin or 5 μg/d CNTF for four days. Real‐time Taqman RT‐PCR was used to quantitatively compare the mRNA levels of selected genes in the ARC‐ME complex. Leptin and CNTF increased ARC‐ME mRNA levels of signal transducer and activator of transcription 3 (STAT3) by 64.5 and 124.7% (p < 0.01), suppressor of cytokine signaling 3 (SOCS3) by 258.9 and 1063.9% (p < 0.01), cocaine and amphetamine regulated transcript (CART) by 102.7 and 123.1% (p < 0.01), and proopiomelanocortin (POMC2) by 374.1 and 264.9% (p < 0.01), respectively. Leptin increased growth hormone releasing hormone (GHRH) by 309.9% (p < 0.01), while CNTF increased janus kinase 2 (JAK2) mRNA by 31.7% (p < 0.01) and decreased gonadotropin releasing hormone 1 (GNRH1) by 59.7% (p < 0.01), mitogen activated protein kinase 1 (MAPK1) by 19.4% (p < 0.05) and tyrosine hydroxylase (TH) by 74.5% (p < 0.05). Significant reduction in daily food intake and body weights by both the treatments was observed. Also, decrease in weights of fat pads was concomitant with lowered serum insulin and leptin levels. Our findings show that leptin and CNTF engage both convergent and divergent pathways involved in feeding, cellular signaling, inflammation, and other related regulatory systems.
NTPDase and 5'‐nucleotidase activities in physiological and disease conditions: New perspectives for human health
Authors: Schetinger Maria Rosa C. , Morsch Vera Maria , Bonan Carla Denise , Wyse Angela T. S.
Published: December 2008

Extracellular nucleotides and nucleosides act as signaling molecules involved in a wide spectrum of biological effects. Their levels are controlled by a complex cell surface‐located group of enzymes called ectonucleotidases. There are four major families of ectonucleotidases, nucleoside triphosphate diphosphohydrolases (NTPDases/CD39), ectonucleotide pyrophosphatase/phosphodiesterases (E‐NPPs), alkaline phosphatases and ecto‐5'‐nucleotidase. In the last few years, substantial progress has been made toward the molecular identification of members of the ectonucleotidase families and their enzyme structures and functions. In this review, there is an emphasis on the involvement of NTPDase and 5'‐nucleotidase activities in disease processes in several tissues and cell types. Brief background information is given about the general characteristics of these enzymes, followed by a discussion of their roles in thromboregulatory events in diabetes, hypertension, hypercholesterolemia and cancer, as well as in pathological conditions where platelets are less responsive, such as in chronic renal failure. In addition, immunomodulation and cell‐cell interactions involving these enzymes are considered, as well as ATP and ADP hydrolysis under different clinical conditions related with alterations in the immune system, such as acute lymphoblastic leukemia (ALL), Bchronic lymphocytic leukemia (B‐CLL) and infections associated with human immunodeficiency virus (HIV). Finally, changes in ATP, ADP and AMP hydrolysis induced by inborn errors of metabolism, seizures and epilepsy are discussed in order to highlight the importance of these enzymes in the control of neuronal activity in pathological conditions. Despite advances made toward understanding the molecular structure of ectonucleotidases, much more investigation will be necessary to entirely grasp their role in physiological and pathological conditions.
Amadori‐glycated albumin‐induced vascular smooth muscle cell proliferation and expression of inhibitor of apoptosis protein‐1 and nerve growth factor‐γ
Authors: Lee Byung‐Wan , Ihm Jahei , Kang Jun Gu , Choi Moon Gi , Yoo Hyung Joon , Ihm Sung‐Hee
Published: December 2008

We investigated the effects of Amadori‐glycated serum albumin (GSA) on cell proliferation as well as expressions of antioxidant enzyme genes and marker genes associated with signal transduction pathways in rat aortic vascular smooth muscle cells (VSMCs). Quiescent VSMCs treated with GSA (0–500 μg/mL, 48 h) exhibited a dose‐dependent increase in proliferation that was prevented by PD98059 (25 μM), suggesting a MAPK‐dependent signaling pathway. Compared with bovine serum albumin (BSA)‐treated cells, the GSA (500 μg/mL, 24 h)‐treated VSMCs showed a higher superoxide dismutase 2 gene expression in quantitative RT‐PCR, suggesting the involvement of oxidative stress. In a focused oligonucleotide array containing 96 signal transduction‐related genes, expression of inhibitor of apoptosis protein‐1 (IAP‐1), nerve growth factorγ (NGF‐γ), and c‐jun genes was significantly higher in the GSA‐treated VSMCs. These results suggest that induction of antiapoptotic proteins like IAP‐1 and strong mitogens like NGF‐γ by GSA might further contribute to the VSMC proliferation and accelerated vascular remodeling in diabetes.
Selenium is critical for cancer‐signaling gene expression but not cell proliferation in human colon Caco‐2 cells
Authors: Zeng Huawei , Botnen James H.
Published: December 2008

Selenium (Se) is a potential anticarcinogenic nutrient, and the essential role of Se in cell growth is well recognized but certain cancer cells appear to have acquired a survival advantage under conditions of Se‐deficiency. To understand the molecular basis of Se‐anticancer effects at nutritional doses (nmol/L) for cultured cells, we generated Se‐deficient colon Caco‐2 cells by gradually reducing serum in media because serum contains a trace amount of Se. The glutathione peroxidase (GPx) activity of Se‐deficient Caco‐2 cells was 10.8 mU/mg protein compared to 133.6 ∼146.3 mU/mg protein in Caco‐2 cells supplemented with 500 nmol/L selenite, SeMSC or SeMet (three tested Se‐chemical forms) after 7‐d culture in serum free media. Interestingly, there were no detectable differences in cell growth, cell cycle progression between Se‐deficient cells and cells supplemented with 500 nmol/L Se. To examine differential cancer signaling‐gene expression between Se‐deficient and Se‐supplemented cells, we employed a cancer signal pathway‐specific array assay coupled with the real time PCR analysis. Our data demonstrate that although Caco‐2 cells are resistant to Se deprivation, Se may exert its anticancer property through increasing the expression of humoral defense gene (A2M) and tumor suppressor‐related genes (IGFBP3, HHIP) while decreasing pro‐inflammatory gene (CXC L9, HSPB2) expression.
BTB/POZ domain of speckle‐type POZ protein (SPOP) confers proapoptotic function in HeLa cells
Authors: Byun Boohyeong , Tak Heejae , Joe Cheol O.
Published: December 2008

The proapoptotic function of SPOP protein was investigated in HeLa cells. HeLa cells underwent apoptosis by the overexpression of SPOP. Studies using SPOP deletion mutants suggest that BTB/POZ domain of SPOP protein is important for the induction of apoptosis in transfected cells. This study first proposes the proapoptotic aspect of the BTB/POZ domain of SPOP protein based on the finding that cells expressing the C‐terminal fragment of SPOP containing the BTB/POZ domain underwent apoptosis.
α‐Tocopherol counteracts ritonavir‐induced proinflammatory cytokines expression in differentiated THP‐1 cells
Authors: Guo Weimin , Zingg Jean Marc , Meydani Mohsen , Azzi Angelo
Published: December 2008

Treatment of HIV‐infected individuals with HIV protease inhibitor (HPI) drugs has significantly increased their life span. However, one of the side effects of HPI drugs is the development of premature atherosclerosis, whose molecular pathogenesis remains unclear. Previously we have reported that α‐tocopherol (α‐T) normalizes CD36 overexpression induced by ritonavir treatment and reduces oxLDL uptake in THP‐1 cells. Since inflammation is a major player in the pathogenesis of atherosclerosis, we hypothesized that HPI drugs, such as ritonavir, increase proinflammatory cytokines synthesis and that α‐T supplementation counteracts this effect by suppressing proinflammatory cytokines levels. Here, we report that after differentiating THP‐1 cells to macrophages, ritonavir treatment (10 μg/mL) significantly increases expression of proinflammatory cytokines, IL‐6, MCP‐1 and IL‐8, at both mRNA and protein levels. This ritonavir‐induced effect is significantly suppressed by treatment of THP‐1/macrophages with 50 μM α‐T. We conclude that ritonavir can induce proinflammatory cytokines synthesis in THP‐1/macrophages, which might be associated with the development of premature atherosclerosis in ritonavir‐treated patients and that this effect is prevented by α‐T.
The influence of folic acid depletion on the Nucleotide Excision Repair capacity of human dermal fibroblasts measured by a modified Host Cell Reactivation Assay
Authors: Burger Katharina , Kieser Nicole , Gallinat S. , Mielke H. , Knott S. , Bergemann Jörg
Published: December 2008

Animal and human studies have shown that low levels of folic acid are associated with an impaired DNA Repair Capacity (DRC) and an increased cancer risk. However, the molecular evidence that folic acid enhances the DRC of cultured human cells is still limited because of a paucity of in vitro studies. We investigated the effect of folic acid depletion in vitro on the DRC of human dermal fibroblasts derived from 17 donors of different ages.

To assess the cellular Nucleotide Excision DRC, we used a modified Host Cell‐Reactivation Assay (HCRA), adapted to the Fluorescence Activated Cell Sorting (FACS)‐technology, which is highly sensitive in comparison to luminometer‐technology and allows single cell based analysis. We used DsRed as a reporter (irradiated with UVC light) and pEGFP to control the performance of the transformations.

Folic acid had a statistically significant effect on the DRC in all of the 17 donors, however, the levels varied considerably between individuals (2.0–19.6%).

When the effect of folic acid substituted on the DRC was compared to donor age, we observed that there was less DNA repair in old donors compared to the younger donors, although this was only significant at lower levels.
Chaga mushroom extract inhibits oxidative DNA damage in lymphocytes of patients with inflammatory bowel disease
Authors: Najafzadeh Mojgan , Reynolds P. Dominic , Baumgartner Adolf , Jerwood David , Anderson Diana
Published: December 2008

Inflammatory Bowel Disease (IBD) is partly caused by oxidative stress from free radicals and reduced antioxidant levels. Using hydrogen peroxide to induce oxidative stress in vitro in peripheral lymphocytes we investigated the induction of DNA damage supplemented with ethanolic extract of Chaga mushroom as a protective antioxidant. Lymphocytes were obtained from 20 IBD patients and 20 healthy volunteers. For treatment, a constant H2 O2 dose (50 μg/ml) was used with variable doses of Chaga extract (10–500 μg/ml). DNA damage was evaluated in 50 cells per individual and dose using the Comet assay (making 1000 observations per experimental point ensuring appropriate statistical power). Chaga supplementation resulted in a 54.9% (p < 0.001) reduction of H2 O2 induced DNA damage within the patient group and 34.9% (p < 0.001) within the control group. Lymphocytes from Crohn's disease (CD) patients had a greater basic DNA damage than Ulcerative Colitis (UC) patients (p < 0.001). Conclusively, Chaga extract reduces oxidative stress in lymphocytes from IBD patients and also healthy individuals when challenged in vitro. Thus, Chaga extract could be a possible and valuable supplement to inhibit oxidative stress in general.