共查询到20条相似文献,搜索用时 31 毫秒
1.
Gunjan Tyagi Shrikant Pradhan Tapasya Srivastava Ranjana Mehrotra 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014
Background
Allicin has received much attention due to its anti-proliferative activity and not-well elucidated underlying mechanism of action. This work focuses towards determining the cellular toxicity of allicin and understanding its interaction with nucleic acid at molecular level.Methods
MTT assay was used to assess the cell viability of A549 lung cancer cells against allicin. Fourier transform infrared (FTIR) and UV-visible spectroscopy were used to study the binding parameters of nucleic acid-allicin interaction.Results
Allicin inhibits the proliferation of cancer cells in a concentration dependent manner. FTIR spectroscopy exhibited that allicin binds preferentially to minor groove of DNA via thymine base. Analysis of tRNA allicin complex has also revealed that allicin binds primarily through nitrogenous bases. Some amount of external binding with phosphate backbone was also observed for both DNA and RNA. UV visible spectra of both DNA allicin and RNA allicin complexes showed hypochromic shift with an estimated binding constant of 1.2 × 104 M- 1 for DNA and 1.06 × 103 M− 1for RNA binding. No major transition from the B-form of DNA and A-form of RNA is observed after their interaction with allicin.Conclusions
The results demonstrated that allicin treatment inhibited the proliferation of A549 cells in a dose-dependent manner. Biophysical outcomes are suggestive of base binding and helix contraction of nucleic acid structure upon binding with allicin.General significance
The results describe cytotoxic potential of allicin and its binding properties with cellular nucleic acid, which could be helpful in deciphering the complete mechanism of cell death exerted by allicin. 相似文献2.
Silvia Castrignanò Sheila J. Sadeghi Gianfranco Gilardi 《Biochimica et Biophysica Acta (BBA)/General Subjects》2012
Background
Nanosized particles of gold are widely used as advanced materials for enzyme catalysis investigations. In some bioanalytical methods these nanoparticles can be exploited to increase the sensitivity by enhancing electron transfer to the biological component i.e. redox enzymes such as drug metabolizing enzymes.Methods
In this work, we describe the characterization of human flavin-containing monooxygenase 3 (hFMO3) in a nanoelectrode system based on AuNPs stabilized with didodecyldimethylammonium bromide (DDAB) on glassy carbon electrodes. Once confirmed by FTIR spectroscopy that in the presence of DDAB-AuNPs the structural integrity of hFMO3 is preserved, the influence of AuNPs on the electrochemistry of the enzyme was studied by cyclic voltammetry and square wave voltammetry.Results
Our results show that AuNPs improve the electrochemical performance of hFMO3 on glassy carbon electrodes by enhancing the electron transfer rate and the current signal-to-noise ratio. Moreover, the electrocatalytic activity of hFMO3-DDAB-AuNP electrodes which was investigated in the presence of two well known substrates, benzydamine and sulindac sulfide, resulted in KM values of 52 μM and 27 μM, with Vmax of 8 nmol min− 1 mg− 1 and 4 nmol min− 1 mg− 1, respectively, which are in agreement with data obtained with the microsomal enzyme.Conclusions
The immobilization of hFMO3 protein in DDAB stabilized AuNP electrodes improves the bioelectrochemical performance of this important phase I drug metabolizing enzyme.General significance
This bio-analytical method can be considered as a promising advance in the development of new techniques suitable for the screening of novel hFMO3 metabolized pharmaceuticals. 相似文献3.
Jaqueline Soares da Silva Sharlene Lopes Pereira Rodolfo do Couto Maia Sharon Schilling Landgraf Celso Caruso-Neves Arthur Eugen Kümmerle Carlos Alberto Manssour Fraga Eliezer Jesus Barreiro Roberto Takashi Sudo Gisele Zapata-Sudo 《Life sciences》2014
Aims
This work investigated the effects of 3,4-methylenedioxybenzoyl-2-thienylhydrazone (LASSBio-294) treatment on the contractile response of soleus (SOL) muscle from rats submitted to myocardial infarction (MI).Main methods
Following coronary artery ligation, LASSBio-294 (2 mg/kg, i.p.) or vehicle was administrated once daily for 4 weeks.Key findings
The run time to fatigue for sham rats was 17.9 ± 2.6 min, and it was reduced to 3.3 ± 0.8 min (P < 0.05) in MI rats. In MI rats treated with LASSBio-294, the time to fatigue was 15.1 ± 3.6 min. During the contractile test, SOL muscles from sham rats showed a response of 7.12 ± 0.54 N/cm2 at 60 Hz, which was decreased to 5.45 ± 0.49 N/cm2 (P < 0.05) in MI rats. The contractility of SOL muscles from the MI-LASSBio-294 group was increased to 9.01 ± 0.65 N/cm2. At 16 mM caffeine, the contractility was reduced from 2.31 ± 0.33 to 1.60 ± 0.21 N/cm2 (P < 0.05) in the MI group. In SOL muscles from MI-LASSBio-294 rats, the caffeine response was increased to 2.62 ± 0.33 N/cm2. Moreover, SERCA2a expression in SOL muscles was decreased by 0.31-fold (31%) in the MI group compared to the Sham group (P < 0.05). In the MI-LASSBio-294 group, it was increased by 1.53-fold (153%) compared to the MI group (P < 0.05). Meanwhile, the nuclear density in SOL muscles was increased in the MI group compared to the Sham group. Treatment with LASSBio-294 prevented this enhancement of cellular infiltrate.Significance
LASSBio-294 treatment prevented the development of muscular fatigue and improved exercise intolerance in rats submitted to MI. 相似文献4.
Balázs Szalontai Gergely Nagy Sashka Krumova Elfrieda Fodor Tibor Páli Stefka G. Taneva Győző Garab Judith Peters András Dér 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
Recently, we have elaborated a thermodynamic theory that could coherently interpret the diverse effects of Hofmeister ions on proteins, based on a single physical parameter, the protein–water interfacial tension (Dér et al., Journal of Physical Chemistry B. 2007, 111, 5344–5350). This theory, implying a “liquid drop model”, predicts changes in protein conformational fluctuations upon addition of Hofmeister salts (containing either kosmotropic or chaotropic anions) to the medium.Methods
Here, we report experimental tests of this prediction using a complex approach by applying methods especially suited for the detection of protein fluctuation changes (neutron scattering, micro-calorimetry, and Fourier-transform infrared spectroscopy).Results
It is demonstrated that Hofmeister salts, via setting the hydrophobic/hydrophilic properties of the protein–water interface, control conformational fluctuations even in the interior of the typical membrane transport protein bacteriorhodopsin, around its temperature-induced, unusual α(II) → α(I) conformational transition between 60 and 90 °C. We found that below this transition kosmotropic (COOCH3−), while above it chaotropic (ClO4−) anions increase structural fluctuations of bR. It was also shown that, in each case, an onset of enhanced equilibrium fluctuations presages this phase transition in the course of the thermotropic response of bR.Conclusions
These results are in full agreement with the theory, and demonstrate that predictions based on protein–water interfacial tension changes can describe Hofmeister effects and interpret protein dynamics phenomena even in unusual cases.General significance
This approach is expected to provide a useful guide to understand the principles governing the interplay between protein interfacial properties and conformational dynamics, in general. 相似文献5.
Flavio Tocci Moreira Silvia Cristina Ramos Andrea Moreira Monteiro Tatiana Helfenstein Magnus Gidlund Nagila Raquel Teixeira Damasceno Antonio Martins Figueiredo Neto Maria Cristina Izar Francisco Antonio Helfenstein Fonseca 《Life sciences》2014
Aims
To compare the effects of two of the most effective lipid-lowering therapies with similar LDL-cholesterol reduction capacity on the innate and adaptive immune responses through the evaluation of autoantibodies anti-oxidized LDL (anti-oxLDL Abs) and electronegative LDL [LDL(−)] levels.Main methods
We performed a prospective, randomized, open label study, with parallel arms and blinded endpoints. One hundred and twelve subjects completed the study protocol and received rosuvastatin 40 mg or ezetimibe/simvastatin 10/40 mg for 12 weeks. Lipids, apolipoproteins, LDL(−), and anti-oxLDL Abs (IgG) were assayed at baseline and end of study.Key findings
Main clinical and laboratory characteristics were comparable at baseline. Lipid modifications were similar in both treatment arms, however, a significant raise in anti-oxLDL Abs levels was observed in subjects treated with rosuvastatin (p = 0.026 vs. baseline), but not in those receiving simvastatin/ezetimibe. (p = 0.233 vs. baseline), thus suggesting modulation of adaptive immunity by a potent statin. Titers of LDL(−) were not modified by the treatments.Significance
Considering atherosclerosis as an immune disease, this study adds new information, showing that under similar LDL-cholesterol reduction, the choice of lipid-lowering therapy can differently modulate adaptive immune responses. 相似文献6.
A. Anitha N. DeepaK.P. Chennazhi Vinoth-Kumar LakshmananR. Jayakumar 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014
Background
Evaluation of the combinatorial anticancer effects of curcumin/5-fluorouracil loaded thiolated chitosan nanoparticles (CRC-TCS-NPs/5-FU-TCS-NPs) on colon cancer cells and the analysis of pharmacokinetics and biodistribution of CRC-TCS-NPs/5-FU-TCS-NPs in a mouse model.Methods
CRC-TCS-NPs/5-FU-TCS-NPs were developed by ionic cross-linking. The in vitro combinatorial anticancer effect of the nanomedicine was proven by different assays. Further the pharmacokinetics and biodistribution analyses were performed in Swiss Albino mouse using HPLC.Results
The 5-FU-TCS-NPs (size: 150 ± 40 nm, zeta potential: + 48.2 ± 5 mV) and CRC-TCS-NPs (size: 150 ± 20 nm, zeta potential: + 35.7 ± 3 mV) were proven to be compatible with blood. The in vitro drug release studies at pH 4.5 and 7.4 showed a sustained release profile over a period of 4 days, where both the systems exhibited a higher release in acidic pH. The in vitro combinatorial anticancer effects in colon cancer (HT29) cells using MTT, live/dead, mitochondrial membrane potential and cell cycle analysis measurements confirmed the enhanced anticancer effects (2.5 to 3 fold). The pharmacokinetic studies confirmed the improved plasma concentrations of 5-FU and CRC up to 72 h, unlike bare CRC and 5-FU.Conclusions
To conclude, the combination of 5-FU-TCS-NPs and CRC-TCS-NPs showed enhanced anticancer effects on colon cancer cells in vitro and improved the bioavailability of the drugs in vivo.General significance
The enhanced anticancer effects of combinatorial nanomedicine are advantageous in terms of reduction in the dosage of 5-FU, thereby improving the chemotherapeutic efficacy and patient compliance of colorectal cancer cases. 相似文献7.
Objectives
Leptin is a hormone secreted from adipocytes. It regulates metabolism and energy homeostasis through the leptin receptor (LEPR) which is localized centrally in hypothalamus as well as in peripheral tissues. The aim of this study was to investigate the association of leptin receptor gene Q223R polymorphism on obesity in association with body mass index (BMI), lipid parameters, plasma leptin levels and homeostasis model assessment of insulin resistance (HOMA-IR).Design and methods
The study included 110 obese and 90 non-obese subjects. The LEPR Q223R polymorphism was determined by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). Plasma leptin levels, serum lipid and antropometric parameters were measured.Results
No association was found between LEPR gene Q223R polymorphism and BMI in both study and control groups. Strikingly study group with non-obese subjects and with the RR genotype (homozygous mutant) had significantly higher serum total cholesterol (p < 0.001) and low density lipoprotein cholesterol (LDL-cholesterol) levels (p < 0.05) than QR (heterozygous) and QQ (wild type) genotypes. In obese group, subjects with the RR genotypes had significantly higher triglycerides (p < 0.05) levels, waist (p < 0.05) and hip circumferences (p < 0.001) than the QQ and QR genotypes.Conclusions
Our results suggest that the LEPR gene Q223R polymorphism has an association with waist and hip circumferences in obese group but no direct association with obesity although there is a significant influence on lipid profile both in obese and non-obese subjects. 相似文献8.
Jing Liu Ju-xiang Liu San-ni Xu Jin-xing Quan Li-min Tian Qian Guo Jia Liu Yun-fang Wang Zhi-yong Shi 《Gene》2012
Aims
L-selectin belongs to selectin family of adhesion molecule and participates in the generation and development of type 2 diabetes (T2D). In this study, we evaluated the relationship between the P213S polymorphism of L-selectin gene and T2D and insulin resistance in the Chinese population.Methods
We genotyped P213S polymorphism in 801 patients with T2D and 834 healthy controls in the Chinese population using polymerase chain reaction–ligase detection reaction (PCR–LDR) technique. Plasma glucose, insulin, lipid, blood urea nitrogen, creatinine and uric acid levels were measured by biochemical technique.Results
The frequency of 213PP genotype and P allele of the L-selectin gene in patients with T2D was significantly higher than that in controls (P = 0.007; P = 0.019, respectively). The relative risk of allele P suffered from T2D was 1.191 times higher than that of allele S. Moreover, the levels of FPG and HOMA-IR of PP and PS genotype carriers were significantly higher than those of SS genotype carriers in the T2D group (P < 0.05).Conclusion
These findings indicated that the P213S polymorphism of L‐selectin gene may contribute to susceptibility to T2D and insulin resistance in the Chinese population, and P allele appears to be a risk factor for T2D. 相似文献9.
Background
Malaria is a devastating disease and Plasmodium falciparum is the most lethal parasite infecting humans. Understanding the biology of this parasite is vital in identifying potential novel drug targets. During every 48-hour intra-erythrocytic asexual replication cycle, a single parasite can produce up to 32 progeny. This extensive proliferation implies that parasites require substantial amounts of lipid precursors for membrane biogenesis. Glycerol kinase is a highly conserved enzyme that functions at the interface of lipid synthesis and carbohydrate metabolism. P. falciparum glycerol kinase catalyzes the ATP-dependent phosphorylation of glycerol to glycerol-3-phosphate, a major phospholipid precursor.Methods
The P. falciparum glycerol kinase gene was disrupted using double crossover homologous DNA recombination to generate a knockout parasite line. Southern hybridization and mRNA analysis were used to verify gene disruption. Parasite growth rates were monitored by flow cytometry. Radiolabelling studies were used to assess incorporation of glycerol into parasite phospholipids.Results
Disruption of the P. falciparum glycerol kinase gene produced viable parasites, but their growth was significantly reduced to 56.5 ± 1.8% when compared to wild type parasites. 14C-glycerol incorporation into the major phospholipids of the parasite membrane, phosphatidylcholine and phosphatidylethanolamine, was 48.4 ± 10.8% and 53.1 ± 5.7% relative to an equivalent number of wild type parasites.Conclusions
P. falciparum glycerol kinase is required for optimal intra-erythrocytic asexual parasite development. Exogenous glycerol may be used as an alternative carbon source for P. falciparum phospholipid biogenesis, despite the lack of glycerol kinase to generate glycerol-3-phosphate.General significance
These studies provide new insight into glycerolipid metabolism in P. falciparum. 相似文献10.
Jessica A.M. Bastiaansen Tian Cheng Mor Mishkovsky João M.N. Duarte Arnaud Comment Rolf Gruetter 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
Acetate metabolism in skeletal muscle is regulated by acetylCoA synthetase (ACS). The main function of ACS is to provide cells with acetylCoA, a key molecule for numerous metabolic pathways including fatty acid and cholesterol synthesis and the Krebs cycle.Methods
Hyperpolarized [1-13C]acetate prepared via dissolution dynamic nuclear polarization was injected intravenously at different concentrations into rats. The 13C magnetic resonance signals of [1-13C]acetate and [1-13C]acetylcarnitine were recorded in vivo for 1 min. The kinetic rate constants related to the transformation of acetate into acetylcarnitine were deduced from the 3 s time resolution measurements using two approaches, either mathematical modeling or relative metabolite ratios.Results
Although separated by two biochemical transformations, a kinetic analysis of the 13C label flow from [1-13C]acetate to [1-13C]acetylcarnitine led to a unique determination of the activity of ACS. The in vivo Michaelis constants for ACS were KM = 0.35 ± 0.13 mM and Vmax = 0.199 ± 0.031 μmol/g/min.Conclusions
The conversion rates from hyperpolarized acetate into acetylcarnitine were quantified in vivo and, although separated by two enzymatic reactions, these rates uniquely defined the activity of ACS. The conversion rates associated with ACS were obtained using two analytical approaches, both methods yielding similar results.General significance
This study demonstrates the feasibility of directly measuring ACS activity in vivo and, since the activity of ACS can be affected by various pathological states such as cancer or diabetes, the proposed method could be used to non-invasively probe metabolic signatures of ACS in diseased tissue. 相似文献11.
Giuseppe Maulucci Diana Troiani Sara Letizia Maria Eramo Fabiola Paciello Maria Vittoria Podda Gaetano Paludetti Massimiliano Papi Alessandro Maiorana Valentina Palmieri Marco De Spirito Anna Rita Fetoni 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014
Background
Noise exposure impairs outer hair cells (OHCs). The common basis for OHC dysfunction and loss by acoustic over-stimulation is represented by reactive oxygen species (ROS) overload that may affect the membrane structural organization through generation of lipid peroxidation.Methods
Here we investigated in OHC different functional zones the mechanisms linking metabolic functional state (NAD(P)H intracellular distribution) to the generation of lipid peroxides and to the physical state of membranes by two photon fluorescence microscopy.Results
In OHCs of control animals, a more oxidized NAD(P)H redox state is associated to a less fluid plasma membrane structure. Acoustic trauma induces a topologically differentiated NAD(P)H oxidation in OHC rows, which is damped between 1 and 6 h. Peroxidation occurs after ~ 4 h from noise insult, while ROS are produced in the first 0.2 h and damage cells for a period of time after noise exposure has ended (~ 7.5 h) when a decrease of fluidity of OHC plasma membrane occurs. OHCs belonging to inner rows, characterized by a lower metabolic activity with respect to other rows, show less severe metabolic impairment.Conclusions
Our data indicate that plasma membrane fluidity is related to NAD(P)H redox state and lipid peroxidation in hair cells.General Significance
Our results could pave the way for therapeutic intervention targeting the onset of redox umbalance. 相似文献12.
Gopalsamy Rajiv Gandhi Antony Stalin Kedike Balakrishna Savarimuthu Ignacimuthu Michael Gabriel Paulraj Rajagopal Vishal 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
The present study was aimed at isolating an antidiabetic molecule from a herbal source and assessing its mechanism of action.Methods
Embelin, isolated from Embelia ribes Burm. (Myrsinaceae) fruit, was evaluated for its potential to regulate insulin resistance, alter β-cell dysfunction and modulate key markers involved in insulin sensitivity and glucose transport using high-fat diet (HFD) fed-streptozotocin (STZ) (40 mg/kg)-induced type 2 diabetic rats. Molecular-dockings were performed to investigate the binding modes of embelin into PPARγ, PI3K, p-Akt and GLUT4 active sites.Results
Embelin (50 mg/kg b wt.) reduced body weight gain, blood glucose and plasma insulin in treated diabetic rats. It further modulated the altered lipid profiles and antioxidant enzymes with cytoprotective action on β-cell. Embelin significantly increased the PPARγ expression in epididymal adipose tissue compared to diabetic control group; it also inhibited adipogenic activity; it mildly activated PPARγ levels in the liver and skeletal muscle. It also regulated insulin mediated glucose uptake in epididymal adipose tissue through translocation and activation of GLUT4 in PI3K/p-Akt signaling cascade. Embelin bound to PPARγ; it disclosed stable binding affinities to the active sites of PI3K, p-Akt and GLUT4.Conclusions
These findings show that embelin could improve adipose tissue insulin sensitivity without increasing weight gain, enhance glycemic control, protect β-cell from damage and maintain glucose homeostasis in adipose tissue.General significance
Embelin can be used in the prevention and treatment of type 2 diabetes mellitus caused due to obesity. 相似文献13.
Background
Some studies suggested that Glutathione S-transferases M1/T1(GSTM1/T1) null polymorphisms may be associated with the risk of vitiligo.Aims
The purpose of this study is to further evaluate the association between GSTM1/T1 null polymorphisms and the susceptibility to vitiligo.Methods
We carried out a retrieval of studies in the databases. Odds ratios (OR) and 95% confidence intervals (95% CIs) were used to assess the strength of this association. We analyzed the data using Stata 11.0.Results
Six case–control studies including 1358 cases and 1673 controls were included in this meta-analysis. Our overall results showed the GSTM1 or GSTT1 null polymorphism was associated with vitiligo (GSTM1:OR = 1.59, 95% CI: 1.21–2.08, P = 0.001; GSTT1: OR = 1.30, 95% CI: 1.12–1.51, P = 0.001). In the subgroup analysis, the GSTM1 null polymorphism might be a genetic risk factor to vitiligo in East Asian (OR = 1.71, 95% CI: 1.12–2.63, P = 0.014) but not in the Mediterranean, however individuals with the GSTT1 null polymorphism in the Mediterranean (OR = 1.76, 95% CI: 1.15–2.71, P = 0.010) but not in East Asian have a greater predisposition to vitiligo. In addition there was also a significant trend toward an association with the combination of the GSTM1 null and GSTT1 null in either East Asians or Mediterraneans.Conclusion
The GSTM1/T1 null polymorphisms may be associated with vitiligo. More studies are needed to confirm this conclusion. 相似文献14.
Yong-han He Wei-lan Kong Guan Wang Yue Zhao Ming-xin Bi Li-xin Na Mao-qing Wang Ben Perry Ying Li 《Gene》2014
Background
We have demonstrated that the calcium-sensing receptor (CaSR) is involved in lipid metabolism; however, whether CaSR polymorphisms affect lipid metabolism in obesity is still unclear. The present study aimed to determine the effects of CaSR polymorphisms on HTG risk in obese Chinese.Methods
A total of 972 subjects with HTG and 1197 with normal triglyceride (NTG) were stratified by body mass index (BMI) into normal weight, overweight or obesity subgroups. After 12-h fasting, CaSR polymorphisms in exon 7 were determined in the blood. Serum lipids and glucose, as well as height, body weight and waist circumference were measured. The anthropometric and metabolic characteristics of the NTG subjects were re-evaluated 3 years later.Results
There were no genotypic or allelic distribution differences for the A986S or Q1011E polymorphisms between the NTG and HTG groups. However, the G/G genotypic and G allelic distributions of the CaSR R990G polymorphism in the HTG group were higher than the NTG group (p < 0.001). After stratification, in obese subjects, the homozygous (G/G) distribution of the CaSR R990G polymorphism in the HTG group was significantly higher than in the NTG group (p = 0.001), and showed an increased risk of HTG at baseline [OR = 2.55, 95% CI = 1.65–3.92, p < 0.006]. Interaction of the CaSR R990G polymorphism with BMI was associated with increased risk of HTG (β = 0.927, p < 0.001). Re-evaluation of the NTG subjects revealed significantly increased serum triglyceride levels in obese homozygous versus wildtype carriers (p < 0.05).Conclusions
These results suggest that the CaSR R990G polymorphism is associated with increased risk of HTG, especially in obese Chinese, and may be a potential genetic predictor of diseases related to HTG. 相似文献15.
Beatriz Tavira Juan Gómez Carmen Díaz-Corte Laura LLobet Eduardo Ruiz-Pesini Francisco Ortega Eliecer Coto 《Gene》2014
Background and aims
Tacrolimus (Tac) is an immunosuppressive drug widely used to avoid organ rejection. New-onset diabetes after transplantation (NODAT) is a major complication among transplanted patients who receive Tac. The increased risk for NODAT could be partly mediated by the effect of Tac on mitochondria from pancreatic beta-cells. Common and rare mitochondrial DNA variants have been linked to the risk of diabetes. Our aim was to determine whether mtDNA polymorphisms/haplogroups were associated with NODAT in Tac-treated kidney transplanted.Methods
Seven polymorphisms that define the common European haplogroups were determined in 115 NODAT and 197 no-NODAT patients.Results
Haplogroup H was significantly more frequent in the NODAT group (50% vs. 35%; p = 0.01, OR = 1.82). There was no difference between patients without and with (n = 106) D2M prior to the transplant.Conclusions
Mitochondrial haplogroup H was associated with the risk for NODAT among Tac-treated transplanted patients. The reported differences between the mtDNA variants could explain the increased NODAT-risk among H-patients. 相似文献16.
Soraia Poloni Sandra Leistner-Segal Isabel Cristina Bandeira Vânia D'Almeida Carolina Fischinger Moura de Souza Poli Mara Spritzer Kamila Castro Tássia Tonon Tatiéle Nalin Apolline Imbard Henk J. Blom Ida V.D. Schwartz 《Gene》2014
Introduction
Classical homocystinuria is a rare genetic disease caused by cystathionine β-synthase deficiency, resulting in homocysteine accumulation. Growing evidence suggests that reduced fat mass in patients with classical homocystinuria may be associated with alterations in choline and homocysteine pathways. This study aimed to evaluate the body composition of patients with classical homocystinuria, identifying changes in body fat percentage and correlating findings with biochemical markers of homocysteine and choline pathways, lipoprotein levels and bone mineral density (BMD) T-scores.Methods
Nine patients with classical homocystinuria were included in the study. Levels of homocysteine, methionine, cysteine, choline, betaine, dimethylglycine and ethanolamine were determined. Body composition was assessed by bioelectrical impedance analysis (BIA) in patients and in 18 controls. Data on the last BMD measurement and lipoprotein profile were obtained from medical records.Results
Of 9 patients, 4 (44%) had a low body fat percentage, but no statistically significant differences were found between patients and controls. Homocysteine and methionine levels were negatively correlated with body mass index (BMI), while cysteine showed a positive correlation with BMI (p < 0.05). There was a trend between total choline levels and body fat percentage (r = 0.439, p = 0.07). HDL cholesterol correlated with choline and ethanolamine levels (r = 0.757, p = 0.049; r = 0.847, p = 0.016, respectively), and total cholesterol also correlated with choline levels (r = 0.775, p = 0.041). There was no association between BMD T-scores and body composition.Conclusions
These results suggest that reduced fat mass is common in patients with classical homocystinuria, and that alterations in homocysteine and choline pathways affect body mass and lipid metabolism. 相似文献17.
Yufeng Qin Xiumei Han Yuzhu Peng Rong Shen Xirong Guo Li Cao Ling Song Jiahao Sha Yankai Xia Xinru Wang 《Gene》2012
Objectives
Epoxide hydrolases are involved in detoxifying and excreting the environmental chemicals, which are associated with decreased semen quality and male infertility. We hypothesized that polymorphisms in epoxide hydrolases may be associated with risk of oligozoospermia and asthenospermia.Design and methods
In this study, 468 fertile controls and 672 idiopathic male infertile patients were recruited. SNPstream and TaqMan assay were used to genotype four single nucleotide polymorphisms in EPHX1 and EPHX2. The semen analysis was performed by computer-assisted semen analysis system.Results
Our results demonstrated that rs1042064 of EPHX2 was significantly associated with decreased risk of oligozoospermia (OR = 0.65, 95% CI: 0.44–0.98) and asthenospermia (OR = 0.66, 95% CI: 0.46–0.94).Conclusions
Our results provided evidence that genetic variants in epoxide hydrolases may modify the risk of oligozoospermia and asthenospermia in Han-Chinese population. 相似文献18.
Éder Ricardo Petry Vinicius Fernandes Cruzat Thiago Gomes Heck Jaqueline Santos Moreira Leite Paulo Ivo Homem de Bittencourt Jr. Julio Tirapegui 《Life sciences》2014
Aims
We hypothesized that oral l-glutamine supplementations could attenuate muscle damage and oxidative stress, mediated by glutathione (GSH) in high-intensity aerobic exercise by increasing the 70-kDa heat shock proteins (HSP70) and heat shock factor 1 (HSF1).Main methods
Adult male Wistar rats were 8-week trained (60-min/day, 5 days/week) on a treadmill. During the last 21 days, the animals were supplemented with either l-alanyl-l-glutamine dipeptide (1.5 g/kg, DIP) or a solution containing the amino acids l-glutamine (1 g/kg) and l-alanine (0.67 g/kg) in their free form (GLN + ALA) or water (controls).Key findings
Plasma from both DIP- and GLN + ALA-treated animals showed higher l-glutamine concentrations and reduced ammonium, malondialdehyde, myoglobin and creatine kinase activity. In the soleus and gastrocnemius muscle of both supplemented groups, l-glutamine and GSH contents were increased and GSH disulfide (GSSG) to GSH ratio was attenuated (p < 0.001). In the soleus muscle, cytosolic and nuclear HSP70 and HSF1 were increased by DIP supplementation. GLN + ALA group exhibited higher HSP70 (only in the nucleus) and HSF1 (cytosol and nucleus). In the gastrocnemius muscle, both supplementations were able to increase cytosolic HSP70 and cytosolic and nuclear HSF1.Significance
In trained rats, oral supplementation with DIP or GLN + ALA solution increased the expression of muscle HSP70, favored muscle l-glutamine/GSH status and improved redox defenses, which attenuate markers of muscle damage, thus improving the beneficial effects of high-intensity exercise training. 相似文献19.
Background
Several single nucleotide polymorphisms (SNPs) in the X-ray cross-complementing group 1 (XRCC1) gene have been shown to influence DNA repair and to modify cancer susceptibility. To investigate the role of these loci further, we examined the association of three XRCC1 polymorphisms with the risk of gliomas in a Han population in northeastern China.Methods
Using a PCR–RFLP method, XRCC1 Arg194Trp, Arg280His and Arg399Gln were genotyped in 624 glioma patients and 580 healthy controls.Results
Significant differences in the distribution of the Arg399Gln allele were detected between glioma patients and healthy controls by a logistic regression analysis (OR = 1.35, 95%CI 1.17–1.68, P = 0.001). Our data also revealed that the Arg399Gln variant (allele A) carriers had an increased glioma risk compared to the wild-type (allele G) homozygous carriers (OR = 1.40, 95%CI 1.12–1.76, P = 0.003).Conclusions
These results suggest that the XRCC1 Arg399Gln might influence the risk of developing glioma in a Han population in northeastern Chinese. 相似文献20.