Lack of association of rs3798220 with small apolipoprotein(a) isoforms and high lipoprotein(a) levels in East and Southeast Asians

OBJECTIVE : The variant allele of rs3798220 in the apolipoprotein(a) gene (LPA) is used to assess the risk for coronary artery disease (CAD) in Europeans, where it is associated with short alleles of the Kringle IV-2 (KIV-2) copy number variation (CNV) and high lipoprotein(a) (Lp(a)) concentrations. No association of rs3798220 with CAD was detected in a GWAS of East Asians. Our study investigated the association of rs3798220 with Lp(a) concentrations and KIV-2 CNV size in non-European populations to explain the missing association of the variant with CAD in Asians. METHODS : We screened three populations from Africa and seven from Asia by TaqMan Assay for rs3798220 and determined KIV-2 CNV sizes of LPA alleles by pulsed-field gel electrophoresis (PFGE). Additionally, CAD cases from India were analysed. To investigate the phylogenetic origin of rs3798220, 40 LPA alleles from Chinese individuals were separated by PFGE and haplotyped for further SNPs. RESULTS : The variant was not found in Africans. Allele frequencies in East and Southeast Asians ranged from 2.9% to 11.6%, and were very low (0.15%) in CAD cases and controls from India. The variant was neither associated with short KIV-2 CNV alleles nor elevated Lp(a) concentrations in Asians. CONCLUSION : Our study shows that rs3798220 is no marker for short KIV-2 CNV alleles and high Lp(a) in East and Southeast Asians, although the haplotype background is shared with Europeans. It appears unlikely that this SNP confers atherogenic potential on its own. Furthermore, this SNP does not explain Lp(a) attributed risk for CAD in Asian Indians.http://www.elsevier.com/locate/atherosclerosis2016-10-31hb2016Chemical Patholog

Chrysin-Enhanced Cytotoxicity of 5-Fluorouracil-Based Chemotherapy for Colorectal Cancer in Mice: Investigating its Effects on Cyclooxygenase-2 Expression

5-fluorouracil (5-FU) has been recognized as an effective medication used to treat colorectal cancer (CRC); however, its administration is facing limitations due to some complications reported. It is also generally accepted that combination therapy is among strategies to improve chemotherapy efficiency. Therefore, chrysin, with its anticancer effects, in combination with 5-FU was investigated in the present study. Azoxymethane (AOM) as a carcinogenic substance along with dextran sodium sulfate (DSS) was additionally utilized to induce CRC in mice. The anticancer effects of chrysin were then evaluated using aberrant crypt foci (ACF) counting and percentage of pathologic lesions in epithelial tissues from distal colon. In this study, cyclooxygenase (COX-2) protein expression was correspondingly explored through immunohistochemistry (IHC). The results revealed that chrysin alone or in combination with 5-FU could decrease ACF counting and percentage of pathologic lesions in comparison with AOM (p<0.05). Moreover, the combination of chrysin (at a dose of 50 mg/kg) with 5-FU reduced COX-2 expression compared with 5-FU alone (p<0.001) or 5-FU in combination with chrysin at a dose of 100 mg/kg (p<0.05). Furthermore, the combined chrysin boosted 5-FU efficiency, so it was suggested as an auxiliary therapy for CRC

Construction of pcDNA3.1-FSHβ expression vector in order to transfer FSHβ gene into a mammalian cellline

Introduction: Follicle stimulating hormone (FSH) is one of the glycoprotein hormones of pituitary gland that consists of two subunits, alpha and beta. Beta subunit has 111 amino acids and a signal peptide, which is consisted of 18 amino acids and it is responsible for biological activity of the hormone. The aim of this study was to construct a pcDNA3.1FSHβ expression vector in order to transfer FSHβ gene into a mammalian cell line.Materials and Methods: To sub-cloning of beta chain from T.vector, a pair of primer was designed that they had a site for EcoRI and HindIII in addition of the start and stop site of the beta chain gene. Amplified beta chain was cloned in pcDNA3.1 at the site of the mentioned enzymes anvd the recombinant plasmid was transformed into E.coli cell. The resulting colonies were checked by PCR re-amplification. The plasmid was purified from some positive colonies. The accuracy of purified plasmids were confirmed by both enzyme digestion and sequencing.Results: Enzyme analysis and sequencing demonstrated that pcDNA3.1-F390β had both correct construction and gene sequence which had an exact correlation with reported FSHβ gene in GenBank.Conclusion: This recombinant plasmid structurally is correct and is proper for transmitting into mammalian cell culture

Lavandula Reduces Heart Injury via Attenuating Tumor Necrosis Factor-Alpha and Oxidative Stress in A Rat Model of Infarct-Like Myocardial Injury

Objective Lavender is used in herbal medicine for different therapeutic purposes. Nonetheless, potential therapeutic effects of this plant in ischemic heart disease and its possible mechanisms remain to be investigated. Materials and Methods In this experimental study, lavender oil at doses of 200, 400 or 800 mg/kg was administered through gastric gavage for 14 days before infarct-like myocardial injury (MI). The carotid artery and left ventricle were cannulated to record arterial blood pressure (BP) and cardiac function. At the end of experiment, the heart was removed and histopathological alteration, oxidative stress biomarkers as well as tumor necrosis factor-alpha (TNF-α) level were evaluated. Results Induction of M.I caused cardiac dysfunction, increased levels of lipid peroxidation, TNF-α and troponin I in heart tissue (P<0.001). Pretreatment with lavender oil at doses of 200 and 400 mg/kg significantly reduced myocardial injury, troponin I and TNF-α. In addition, it improved cardiac function and antioxidant enzyme activity (P<0.01). Conclusion Our finding showed that lavender oil has cardioprotective effect through inhibiting oxidative stress and inflammatory pathway in the rat model with infarct-like MI. We suggest that lavender oil may be helpful in prevention or attenuation of heart injury in patients with high risk of myocardial infarction and/or ischemic heart disease

Enhanced efficacy of 5-fluorouracil combined with chrysin in treating colorectal cancer in BALB/c mice: Impact on β-catenin and inducible nitric oxide synthase expression

229-236Chrysin is a naturally occurring bioflavonoid found in honey and propolis, with anti-cancer and anti-inflammatory properties. This study aimed to investigate the therapeutic effect of chrysin combined with 5-fluorouracil (5-FU) in the treatment of mice with colorectal cancer (CRC). Moreover, the effects of these two compounds on the expression of β-catenin and inducible nitric oxide synthase (iNOS) were investigated. The CRC was induced in the mice by azoxymethane (AOM). The co-administration of 5-FU and chrysin in the treatment of mice reduced the number of aberrant crypt foci (ACF) and the pathologic lesion percentage compared to other treatment groups (P <0.05). The co-administration of 5-FU and chrysin resulted in a reduction in β-catenin and iNOS (P <0.05). We showed that a combination of 5-FU and chrysin is superior to 5-FU or chrysin alone in the treatment of mice with CRC. Our approach opens an avenue to introduce a useful therapeutic option for colorectal cancer in humans

Protective Effects of Crocus Sativus L. Extract and Crocin against Chronic-Stress Induced Oxidative Damage of Brain, Liver and Kidneys in Rats

Purpose: Chronic stress has been reported to induce oxidative damage of the brain. A few studies have shown that Crocus Sativus L., commonly known as saffron and its active constituent crocin may have a protective effect against oxidative stress. The present work was designed to study the protective effects of saffron extract and crocin on chronic – stress induced oxidative stress damage of the brain, liver and kidneys. Methods: Rats were injected with a daily dose of saffron extract (30 mg/kg, IP) or crocin (30 mg/kg, IP) during a period of 21 days following chronic restraint stress (6 h/day). In order to determine the changes of the oxidative stress parameters following chronic stress, the levels of the lipid peroxidation product, malondialdehyde (MDA), the total antioxidant reactivity (TAR), as well as antioxidant enzyme activities glutathione peroxidase (GPx), glutathione reductase (GR) and superoxide dismutase (SOD) were measured in the brain, liver and kidneys tissues after the end of chronic stress. Results: In the stressed animals that receiving of saline, levels of MDA, and the activities of GPx, GR, and SOD were significantly higher (P<0.0001) and the TAR capacity were significantly lower than those of the non--stressed animals (P<0.0001). Both saffron extract and crocin were able to reverse these changes in the stressed animals as compared with the control groups (P<0.05). Conclusion: These observations indicate that saffron and its active constituent crocin can prevent chronic stress–induced oxidative stress damage of the brain, liver and kidneys and suggest that these substances may be useful against oxidative stress

In vivo antioxidant and kidney protective potential of Atorvastatin against cadmium chloride-induced kidney injury in male Wistar rat

Cadmium contributes to nephrotoxicity linked with oxidative stress in humans and animals. This study used Atorvastatin to examine its effect on cadmium chloride-induced nephrotoxicity in a rat model using biochemical and histological methodologies. Experiments were performed on 56 adult male Wistar rats (200 ± 20 g), randomly assigned to eight groups. Rats in Group A received physiologic saline. Group B was treated with a dosage of 20 mg/ kg body weight/day AT for 15 days. Groups C, D, and E received CdCl2 with dosages of 1, 2, and 3 mg/kg body weight, respectively. Groups F, G, and H were pretreated with Atorvastatin, 30 min prior to the administration of CdCl2. Rats received intra-gastric Atorvastatin for 15 days during which cadmium chloride was given from days 8 to 15. On day 16, blood samples were collected, and kidneys were excised to evaluate the biochemical and histopathological changes. Cadmium chloride significantly increased malondialdehyde (MDA), serum creatinine (Cr), blood urea nitrogen (BUN), and decreased superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GPx) levels. Administration of Atorvastatin (20 mg/kg) significantly decreased lipid peroxidation, BUN and Cr, while it significantly increased glutathione and antioxidant enzymes activity. Atorvastatin improved the histological changes and all biochemical markers and shed light on its protecting role against cadmium chloride-induced oxidative stress in the kidney

Lack of association of rs3798220 with small apolipoprotein(a) isoforms and high lipoprotein(a) levels in East and Southeast Asians

OBJECTIVE : The variant allele of rs3798220 in the apolipoprotein(a) gene (LPA) is used to assess the risk for coronary artery disease (CAD) in Europeans, where it is associated with short alleles of the Kringle IV-2 (KIV-2) copy number variation (CNV) and high lipoprotein(a) (Lp(a)) concentrations. No association of rs3798220 with CAD was detected in a GWAS of East Asians. Our study investigated the association of rs3798220 with Lp(a) concentrations and KIV-2 CNV size in non-European populations to explain the missing association of the variant with CAD in Asians. METHODS : We screened three populations from Africa and seven from Asia by TaqMan Assay for rs3798220 and determined KIV-2 CNV sizes of LPA alleles by pulsed-field gel electrophoresis (PFGE). Additionally, CAD cases from India were analysed. To investigate the phylogenetic origin of rs3798220, 40 LPA alleles from Chinese individuals were separated by PFGE and haplotyped for further SNPs. RESULTS : The variant was not found in Africans. Allele frequencies in East and Southeast Asians ranged from 2.9% to 11.6%, and were very low (0.15%) in CAD cases and controls from India. The variant was neither associated with short KIV-2 CNV alleles nor elevated Lp(a) concentrations in Asians. CONCLUSION : Our study shows that rs3798220 is no marker for short KIV-2 CNV alleles and high Lp(a) in East and Southeast Asians, although the haplotype background is shared with Europeans. It appears unlikely that this SNP confers atherogenic potential on its own. Furthermore, this SNP does not explain Lp(a) attributed risk for CAD in Asian Indians.http://www.elsevier.com/locate/atherosclerosis2016-10-31hb2016Chemical Patholog