Journal of applied biomedicine最新文献

The potency of three nerve agents (sarin, soman, tabun) to induce oxidative damage of DNA in lymphocytes, liver and brain during lethal or sublethal poisoning was investigated. The single strand breaks or oxidative base DNA damage was evaluated with the help of Comet assay and a specific enzyme able to detect oxidative bases of DNA (endonuclease III). While sarin and soman administered at sublethal doses corresponding to 50% of their LD50 values were not able to induce oxidative damage of DNA, their lethal dose (LD50) induced the significant increase of the number of oxidative bases in DNA of hepatocytes. In addition, tabun administered at lethal dose (LD50) induced significant increase of the number of single strand breaks and oxidative bases of DNA in glial cells isolated from pontomedullar brain region. Thus, some nerve agents were able to induce oxidative damage in the peripheral as well as central compartment but only in the case of severe poisoning caused by lethal doses of nerve agents. This non-cholinergic effect of nerve agents has probably consequences with nerve agents-induced hypoxic status during acute cholinergic crisis and it can contribute to their long-term toxic effects.

Embryonic stem (ES) cells are pluripotent cells widely used in cell therapy and tissue engineering. However, the broader clinical applications of ES cells are limited by their genomic instability and karyotypic abnormalities. Thus, understanding the mechanisms underlying ES cell karyotypic abnormalities is critical to optimizing their clinical use. In this study, we focused on proliferating human and mouse ES cells undergoing multipolar divisions. Specifically, we analyzed the frequency and outcomes of such divisions using a combination of time-lapse microscopy and cell tracking. This revealed that cells resulting from multipolar divisions were not only viable, but they also frequently underwent subsequent cell divisions. Our novel data also showed that in human and mouse ES cells, multipolar spindles allowed more robust escape from chromosome segregation control mechanisms than bipolar spindles. Considering the frequency of multipolar divisions in proliferating ES cells, it is conceivable that cell division errors underlie ES cell karyotypic instability.

Cardiac resynchronization therapy is an effective and widely accessible treatment for patients with advanced, drug-refractory heart failure. It has been shown to reverse maladaptive ventricular remodeling, increase exercise capacity, and lower hospitalization and mortality rates. However, there still exists a considerable proportion of patients who do not respond favorably to the therapy. Tailored left ventricular (LV) lead positioning instead of empiric implantation is thought to have the greatest potential to increase response rates. In our paper, we focus on the rationale for guided LV lead implantation and provide a review of the non-invasive imaging modalities applicable for navigation during LV lead implantation, with special attention to the latest achievements in the field of multimodality imaging and image fusion techniques. Current limitations and future perspectives of the concept are discussed as well.

Examination of semen characteristics is routinely performed for fertility status investigation of the male partner of an infertile couple as well as for evaluation of the sperm donor candidate. A useful tool for preliminary assessment of semen characteristics might be an artificial neural network. Thus, the aim of the present study was to construct an artificial neural network, which could be used for predicting the result of semen analysis based on the basic questionnaire data. On the basis of eleven survey questions two models of artificial neural networks to predict semen parameters were developed. The first model aims to predict the overall performance and profile of semen. The second network was developed to predict the concentration of sperm. The network to evaluate sperm concentration proved to be the most efficient. 92.93% of the patients in the learning process were properly qualified for the group with a correct or incorrect result, while the result for the test set was 85.71%. This study suggests that an artificial neural network based on eleven survey questions might be a valuable tool for preliminary evaluation and prediction of the semen profile.

Exploration of motor cortex activity is essential to understanding the pathophysiology in Parkinson's Disease (PD), but only simple motor tasks can be investigated using a fMRI or PET. We aim to investigate the cortical activity of PD patients during a complex motor task (gait) to verify the impact of deep brain stimulation in the subthalamic nucleus (DBS-STN) by using Near-Infrared-Spectroscopy (NIRS). NIRS is a neuroimaging method of brain cortical activity using low-energy optical radiation to detect local changes in (de)oxyhemoglobin concentration. We used a multichannel portable NIRS during finger tapping (FT) and gait. To determine the signal activity, our methodology consisted of a pre-processing phase for the raw signal, followed by statistical analysis based on a general linear model. Processed recordings from 9 patients were statistically compared between the on and off states of DBS-STN. DBS-STN led to an increased activity in the contralateral motor cortex areas during FT. During gait, we observed a concentration of activity towards the cortex central area in the "stimulation-on" state. Our study shows how NIRS can be used to detect functional changes in the cortex of patients with PD with DBS-STN and indicates its future use for applications unsuited for PET and a fMRI.

In traditional medicine, natural silk is regarded as a cognitive enhancer and a cure for ameliorating the symptoms of heart disease, atherosclerosis, and metabolic disorders. In this review, general characteristics of both silk proteins, fibroin and sericin, extracted from silkworm Bombyx mori and their potential use in the neuronal disorders was discussed. Evidence shows that silk proteins exhibit neuroprotective effects in models of neurotoxicity. The antioxidant, neuroprotective, and acetylcholinesterase inhibitory mechanisms of silk proteins could prove promising in the treatment of neurodegenerative diseases. Owing to their excellent neurocompatibility and physicochemical properties, silk proteins have been used as scaffolds and drug delivery materials in the neuronal tissue engineering. These data support the potential of silk proteins as an effective complementary agent for central and peripheral neurological disorders.

Idiopathic scoliosis (IS) is a common medical condition in children, characterized by three-dimensional spinal curve and strong evidence of genetic predisposition. The purpose of the present case-control study is to examine the association between the polymorphic variant rs11190870 (T/C), near the LBX1 gene, and IS predisposition in distinct subgroups based on age at onset, family history and gender. A total of 127 IS patients and 254 unrelated controls of Southeastern European descent were recruited. The genotyping was carried out by TaqMan real-time amplification technology. The results were analyzed by the Pearson's Chi-squared Test and the Fisher's Exact Test with a value of p less than 0.05 as statistically significant. The T allele and homozygous TT genotype were associated with a greater incidence of IS. Our results suggest that there is a genetic association with IS in adolescents, familial and non-familial cases, and in females. Larger case-control studies are necessary to examine the genetic factors of IS/AIS etiology in infants, juveniles and males. In conclusion, the molecular genetic identification of diagnostic and prognostic molecular markers would make an early treatment including minimally invasive procedures possible.

This study investigates serum redox status and adenosine catabolism markers in relation to tumor and angiogenesis, in patients with gallbladder carcinoma (GBC). The level of adenosine deaminase (ADA) and xanthine oxidase (XO) activities, nitrites (NO2^-), glutathione (GSH) and malondialdehyde (MDA) were measured in sera of 40 GBC patients and 40 healthy donors. In parallel, 15 tumors at TNM stage IV were scored for CD34 expression and microvessel density (MVD). The results showed that XO and ADA activities, nitrites and MDA levels enhanced by 1.26 (p < 0.01), 2.69, 2.0, and 3.2-fold (p < 0.001), respectively, while those of GSH decreased by 44.6% (p < 0.001). According to receiver operating characteristic (ROC) curve, the optimal cut-off for XO, ADA, MDA, GSH and nitrites were 5.41U/l, 17.02 U/l, 3.72 μM, 36.91 μM and 21.21 μM, respectively. Spearman correlation revealed that ADA activity correlated to nitrites levels (r = 0.3419, p < 0.05) and XO activity (r = 0.5487, p < 0.001). Multivariate binary logistic regression analysis revealed that MDA (OR = 5.78, p < 0.05), ADA (OR = 1.28, p < 0.001) and XO (OR = 2.81, p < 0.05) correlated positively to GBC. CD34 was up expressed in 73.3% of tumors at intermediate to high levels. Multiple regression analysis showed that ADA affected MVD (r = 0.604, p < 0.01). The results suggest that high MDA/GSH ratio is a potential biomarker of GBC. In addition, the oxidative adenosine catabolism indicated that active purine salvage pathway could support tumor progression by sustaining angiogenesis.

The advanced glycated end products (AGEs) are formed in the diabetic patients; it is a major cause of macrovascular and microvascular complications in diabetes. Clinically there is no treatment available for the AGEs. Stveoside (Stv), a sweetener has potent anti-diabetic and anti-oxidant activity. Hence, we investigated its use in prevention of AGEs formation using in vitro and in vivo models. Diabetes was induced by streptozotocin (STZ). These rats were kept without treatment till blood HbA1c was markedly increased. They were then divided into 5 groups and treated orally with vehicle or Metformin (MET) or Stv respectively for 28 days. Every 7th day, animals were tested for body weight and blood glucose (BG). On the last day of treatment, all the groups were evaluated for physiological and biochemical parameters, histopathology and AGEs; N-carboxymethyl-lysine (CML) estimation. Stv showed inhibition of AGEs in in vitro as well as in in vivo respectively. Positive effects were seen on the BG, lipid profile and urine parameters as well it showed reduced formation of CML. It also showed antihyperglycaemic, antihyperlipedemic and nephroprotective activities. The present study provides scientific rationale for the use of Stv as a sweetener with additional benefits in diabetes.

2-chloroethyl ethyl sulfide (CEES) is a vesicant agent, commonly referred to half mustard due to its ability to form monofunctional adducts with DNA. In this study, we evaluated the chemoprotective potential of 13 compounds and their mixtures with sodium 2-mercaptoethanesulfonate (MESNA) against CEES-induced geno- and cytotoxicity in human lung cell line A-549. MESNA, L-glutathione (GSH), thiourea, sodium thiosulfate, hexamethylenetetramine, 4-acetamidophenol, asoxime dichloride (HI-6), N-acetyl-L-cysteine (NAC), sodium pyruvate, myo-inositol, 3-aminobenzamide (3-AB), nicotinamide, and Nω-nitro-L-arginine methyl ester hydrochloride and combinations of these compounds with MESNA were applied 30 min before CEES. DNA alkylation was measured using modified comet assay 1 and 24 h after the exposure. Cell viability was determined using MTT assay at 24 and 72 h. The mono-therapeutical approach identified MESNA and GSH to provide significant chemoprotection. NAC and 3-AB supported DNA damage repair, while cell viability remained unaffected. Mixtures of GSH or NAC with MESNA showed protective synergism against DNA damage. Other compounds or their combinations with MESNA failed due to the potentiation of CEES-induced cytotoxicity. The chemoprotection against CEES remains limited; however, the combination of substances can provide protective synergy and may represent a promising strategy in the treatment of accidental exposure to monoalkylating agents.