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141.
The pro-mutagenicity of chemically-induced methylation of DNA at the O6 position of dexoyguanosine was studied in cultured adult rat liver epithelial cells. To modify the level of O6-methyldeoxyguanosine (O6-medGuo) resulting from exposure to an alkylating agent, partial depletion of the O6-alkylguanine-DNA alkyltransferase (AGT) repair system was produced by pretreatment of ARL 18 cells with a non-toxic dose of exogenous O6-methylguanine (O6-meG). Exposure of cells to 0.6 mM O6-meG for 4 h depleted AGT activity by about 40%. Intact and pretreated cells were exposed to a range of doses of N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), and mutagenesis at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus was quantified by measurement of 6-thioguanine-resistant mutants. The mutagenicity of MNNG was dose dependent and was greater in O6-meG pretreated cultures than in intact cultures. Immunoslot blot measurement of O6-medGuo employing a mouse monoclonal antibody demonstrated that MNNG produced O[su6-medGuo and that the intact liver cells were efficient in eliminating this lesion from their DNA. Since depletion of AGT would be expected to affect the rate of elimination of only O6-medGuo, it is concluded that this lesion is highly pro-mutagenic. 相似文献
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143.
Kanwar Nasir M. Khan Gary J. Kociba Maxey L. Wellman Jolene A. Reiter 《In vitro cellular & developmental biology. Animal》1992,28(4):260-266
Summary The pathogenesis of retrovirus-induced erythroid aplasia in cats is unknown. In studies to define mechanisms of cytotoxicity
associated with retroviral infections, bone marrow mononuclear cells (BMMC) from healthy specific pathogenfree cats were co-cultured
with uninfected feline embryonic fibroblasts (FEA cells) and FEA cells infected with feline leukemia virus (FeLV) of subgroup
A (FEA-A) or subgroup C (FEA-C). Moderate to marked cytotoxicity (CPE) developed in co-cultures of BMMC and FEA-C cells on
Days 5 to 7 of incubation but not in co-cultures of BMMC and FEA-A or BMMC and uninfected cells (FEA-CT). Cytotoxicity was
associated with adherent cells of light density (1.056) from bone marrow and peripheral blood, which were positive for alpha
naphthyl butyrate esterase activity. Stimulation of adherent cells with phorbol ester or addition of recombinant human tumor
necrosis factor-alpha (rhTNF-α) caused similar CPE in FEA-CT cells. The TNF-α concentrations in the culture supernatants of BMMC+FEA-C were higher than those of BMMC+FEA-A or BMMC+FEA-CT, and addition
of anti-TNF antibodies to the cultures blocked the CPE. These data support the hypothesis that macrophages exposed to FeLV-C
cause CPE in co-cultures of BMMC and FEA cells by a mechanism involving TNF-α. It is suggested that TNF-α may be involved in the suppression of hematopoiesis in cats which develop FeLV-C induced erythroid aplasia. 相似文献
144.
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146.
One‐year outcomes of an intense workplace cardio‐metabolic risk reduction program among high‐risk employees: The My Unlimited Potential
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Henry Guzman Sankalp Das Doris Brown Chukwuemeka U. Osondu Erica Spatz Brandon Shaffer Joann Santiago‐Charles Teresa Ochoa Joseph Mora Cynthia Gilliam Virginia Lehn Shoshana Sherriff Thinh H. Tran Janisse Post Emir Veledar Theodore Feldman Arthur S. Agatston Khurram Nasir 《Obesity (Silver Spring, Md.)》2016,24(1):71-78
147.
Lihua Zhang Jing Li Xi Li Khurram Nasir Haibo Zhang Yongjian Wu Shuang Hu Qing Wang Nicholas S. Downing Nihar R. Desai Frederick A. Masoudi John A. Spertus Harlan M. Krumholz Lixin Jiang China PEACE Collaborative Group 《PloS one》2016,11(4)
BackgroundStatin therapy is among the most effective treatments to improve short- and long-term mortality after acute myocardial infarction. The use of statin, and the intensity of their use, has not been described in acute myocardial infarction patients in China, a country with a rapidly growing burden of cardiovascular disease.ConclusionsThe use of statin therapy has dramatically increased over the past decade in Chinese patients with acute myocardial infarction. However, half of patients still did not receive intensive statin therapy in 2011.Given that guidelines strongly endorse intensive statin therapy for acute myocardial infarction patients, initiatives promoting the use of statin therapy, with attention to treatment intensity, would support further improvements in practice. 相似文献
148.
Bushra Irum Shahid Y. Khan Muhammad Ali Haiba Kaul Firoz Kabir Bushra Rauf Fareeha Fatima Raheela Nadeem Arif O. Khan Saif Al Obaisi Muhammad Asif Naeem Idrees A. Nasir Shaheen N. Khan Tayyab Husnain Sheikh Riazuddin Javed Akram Allen O. Eghrari S. Amer Riazuddin 《PloS one》2016,11(11)
PurposeTo identify the molecular basis of non-syndromic autosomal recessive congenital cataracts (arCC) in a consanguineous family.MethodsAll family members participating in the study received a comprehensive ophthalmic examination to determine their ocular phenotype and contributed a blood sample, from which genomic DNA was extracted. Available medical records and interviews with the family were used to compile the medical history of the family. The symptomatic history of the individuals exhibiting cataracts was confirmed by slit-lamp biomicroscopy. A genome-wide linkage analysis was performed to localize the disease interval. The candidate gene, LIM2 (lens intrinsic membrane protein 2), was sequenced bi-directionally to identify the disease-causing mutation. The physical changes caused by the mutation were analyzed in silico through homology modeling, mutation and bioinformatic algorithms, and evolutionary conservation databases. The physiological importance of LIM2 to ocular development was assessed in vivo by real-time expression analysis of Lim2 in a mouse model.ResultsOphthalmic examination confirmed the diagnosis of nuclear cataracts in the affected members of the family; the inheritance pattern and cataract development in early infancy indicated arCC. Genome-wide linkage analysis localized the critical interval to chromosome 19q with a two-point logarithm of odds (LOD) score of 3.25. Bidirectional sequencing identified a novel missense mutation, c.233G>A (p.G78D) in LIM2. This mutation segregated with the disease phenotype and was absent in 192 ethnically matched control chromosomes. In silico analysis predicted lower hydropathicity and hydrophobicity but higher polarity of the mutant LIM2-encoded protein (MP19) compared to the wild-type. Moreover, these analyses predicted that the mutation would disrupt the secondary structure of a transmembrane domain of MP19. The expression of Lim2, which was detected in the mouse lens as early as embryonic day 15 (E15) increased after birth to a level that was sustained through the postnatal time points.ConclusionA novel missense mutation in LIM2 is responsible for autosomal recessive congenital cataracts. 相似文献
149.
Rabail H. Toor Shabana Malik Haleema Qamar Faiza Batool Maira Tariq Zainab Nasir Raazia Tassaduq Jane B. Lian Janet L. Stein Gary S. Stein Abdul R. Shakoori 《Journal of cellular physiology》2019,234(12):23082-23096
In continuation of the investigation of osteogenic potential of solvent fractions of ethanolic extract of Cissus quadrangularis (CQ), an ancient medicinal plant, most notably known for its bone-healing properties, to isolate and identify antiosteoporotic compounds. In the current study, we report the effect of hexane fraction (CQ-H) and dichloromethane fraction (CQ-D) of CQ on the differentiation and mineralization of mouse preosteoblast cell line MC3T3-E1 (subclone 4). Growth, viability, and proliferation assays revealed that low concentrations (0.1, 1, and 100 ng/ml) of both solvent fractions were nontoxic, whereas higher concentrations were toxic to the cells. Differentiation and mineralization of MC3T3-E1 with nontoxic concentrations of CQ-D and CQ-H revealed that CQ-D delayed the mineralization of MC3T3-E1 cells. However, early and enhanced mineralization was observed in cultures treated with nontoxic concentrations of CQ-H, as indicated by Von Kossa staining and expression profile of osteoblast marker genes such as osterix, Runx2, alkaline phosphatase (ALP), collagen (Col1a1), integrin-related bone sialoprotein (IBSP), osteopontin (OPN), and osteocalcin (OCN). These findings suggest CQ-H as the most efficacious solvent fraction for further investigation to isolate and identify the active compounds in CQ-H. 相似文献
150.
Kanwal Rehman Tahir Ali Chohan Iqra Waheed Zeeshan Gilani Muhammad Sajid Hamid Akash 《Journal of cellular biochemistry》2019,120(1):425-438
There has been a dramatic increase in the prevalence of diabetes mellitus (DM) and its associated complications globally. The postprandial stage of DM involves prompt elevation in the levels of blood glucose and α-amylase, a carbohydrate-metabolizing enzyme is mainly involved in the regulation of postprandial hyperglycemia. This study was designed to assess the ability of a well-known flavonoid, taxifolin (TFN), against postprandial hyperglycemia and its inhibitory effects on α-amylase activity through the assessment of therapeutic potentials of TFN in an alloxan-induced diabetic animal model. The binding potential TFN with an α-amylase receptor was also investigated through molecular dynamics (MD) simulation and docking of to compare the binding affinities and energies of TFN and standard drug acarbose (ACB) with target enzyme. TFN significantly improved the postprandial hyperglycemia, lipid profile, and serum levels of α-amylase, lipase, and C-reactive protein in a dose-dependent manner when compared with that of either DM-induced and ACB-treated alloxan-induced diabetic rats. Moreover, TFN also enhanced the anti-oxidant status and normal functioning of the liver in alloxan-induced diabetic rats more efficiently as compared to that of ACB-treated alloxan-induced diabetic rats. Therapeutic potentials of TFN were also verified by MD simulation and docking results, which exhibited that the binding energy and affinity of TFN to bind with receptor was significantly higher as compared to that of ACB. Hence, the results of this study signify that TFN might be a potent inhibitor of α-amylase that has the potential to regulate the postprandial hyperglycemia along with its anti-inflammatory and anti-oxidant properties during the treatment of DM. 相似文献