The Effects of Supplementation with Probiotic on Biomarkers of Oxidative Stress in Adult Subjects: a Systematic Review and Meta-analysis of Randomized Trials

Probiotics and Antimicrobial Proteins - Previous studies have supposed that probiotic supplementation led to a positive effect on different health outcomes. Furthermore, several studies indicated...     

Assessment of Water Quality of Soan River using Physicochemical Parameters and Aquatic Insects Diversity

Biology Bulletin - In the present study, the effect of pollutants produced by human dwelling, agricultural and industrial activities on aquatic invertebrate’s communities of Soan River,...     

Association of total energy intake,diet quality and sleep disorders in university-term female students

Sleep and Biological Rhythms - The aim of this study is to determine the relationship between diet quality and overall sleep quality, sleep duration, and presence of insomnia in the university-term...     

Preservation of musical memory in an amnesic professional cellist

Learning and memory of music involves a multitude of perceptual, motor, affective, and autobiographical memory processes [1]. Patient and imaging studies suggest that musical memory may involve distinct neural substrates [2,3]. However, the degree of independence of such a system from other memory domains is controversial [4]. We have investigated a 68-year-old professional cellist, patient PM, who developed severe amnesia following encephalitis. This case provided a unique opportunity to study musical memory in a patient with a precisely defined premorbid musical knowledge and well-demarcated focal lesions of the brain. Despite severe memory impairments, he performed like healthy musicians in various tests of recognition memory for music. These findings suggest that learning and retention of musical information depends on brain networks distinct from those involved in other types of episodic and semantic memory.     

Involvement of notch signaling in wound healing

The Notch signaling pathway is critically involved in cell fate decisions during development of many tissues and organs. In the present study we employed in vivo and cell culture models to elucidate the role of Notch signaling in wound healing. The healing of full-thickness dermal wounds was significantly delayed in Notch antisense transgenic mice and in normal mice treated with gamma-secretase inhibitors that block proteolytic cleavage and activation of Notch. In contrast, mice treated with a Notch ligand Jagged peptide showed significantly enhanced wound healing compared to controls. Activation or inhibition of Notch signaling altered the behaviors of cultured vascular endothelial cells, keratinocytes and fibroblasts in a scratch wound healing model in ways consistent with roles for Notch signaling in wound healing functions all three cell types. These results suggest that Notch signaling plays important roles in wound healing and tissue repair, and that targeting the Notch pathway might provide a novel strategy for treatment of wounds and for modulation of angiogenesis in other pathological conditions.     

Expression of human cytochrome p450 3A4 gene in Schizosaccharomyces pombe

Heterologous expression systems can be utilized to great advantage in the study of cytochrome P450 enzymes. P450 3A4 is one of the major forms of cytochrome P450 found in liver. It is also involved in the metabolism of numerous widely used drugs and xenobiotics. In the present study human liver cytochrome P450 3A4 gene was transferred into the fission yeast Schizosaccharomyces pombe via two different S. pombe expression vectors carrying thiamine repressible promoter — nmt1 (pREP42) and constitutive promoter — adh1 (pART1). Heterologously expressed cytochrome P450 3A4 was detected in the cells grown in minimal (EMM) or rich medium (YEL) containing 0.5% (w/v) glucose. A typical cytochrome P450 peak for 3A4 was observed at 448 nm in microsomal fraction. The presence of heterologous expression of 3A4 form was also determined by SDS-PAGE and it molecular mass was identified as 52 kDa. The enzyme activity was confirmed by HPLC analysis, using testosterone as substrate.     

Allosteric modulation of human P-glycoprotein. Inhibition of transport by preventing substrate translocation and dissociation

The human multidrug transporter P-glycoprotein (Pgp, ABCB1) contributes to the poor bioavailability of many anticancer and antimicrobial agents as well as to drug resistance at the cellular level. For rational design of effective Pgp inhibitors, a clear understanding of its mechanism of action and functional regulation is essential. In this study, we demonstrate that inhibition of Pgp-mediated drug transport by cis-(Z)-flupentixol, a thioxanthene derivative, occurs through an allosteric mechanism. Unlike competitive inhibitors, such as cyclosporin A and verapamil, cis-(Z)-flupentixol does not interfere with substrate ([(125)I]iodoarylazidoprazosin) recognition by Pgp, instead it prevents substrate translocation and dissociation, resulting in a stable but reversible Pgp-substrate complex. cis-(Z)-Flupentixol-induced complex formation requires involvement of the Pgp substrate site, because agents that either physically compete (cyclosporin A) for or indirectly occlude (vanadate) the substrate-binding site prevent formation of the complex. Allosteric modulation by cis-(Z)-flupentixol involves a conformational change in Pgp detectable by monoclonal antibody UIC2 binding to a conformation-sensitive external epitope of Pgp. The conformational change observed is distinct from that induced by Pgp substrates or competitive inhibitors. A single amino acid substitution (F983A) in TM12 of Pgp that impairs inhibition by cis-(Z)-flupentixol of Pgp-mediated drug transport also affects stabilization of the Pgp-substrate complex as well as the characteristic conformational change. Taken together, our results describe the molecular mechanism by which the Pgp modulator cis-(Z)-flupentixol allosterically inhibits drug transport.     

Significance of low-dose and standard-dose ACTH tests compared to overnight metyrapone test in the diagnosis of adrenal insufficiency in childhood

OBJECTIVE: To discover the value of low-dose (LDAT) and standard-dose ACTH tests (SDAT) as compared with the metyrapone test in the diagnosis of secondary adrenal insufficiency. PATIENTS AND METHODS: LDAT (0.5 microg/m2), SDAT (250 microg/m2) and overnight metyrapone (30 mg/kg) tests were carried out in 29 patients with suspected adrenal insufficiency. LDAT and SDAT were also performed in 36 control subjects. RESULTS: 18 of 29 patients were grouped in the adrenal-sufficient (AS) group and 11 of 29 patients in the adrenal-deficient (AD) group according to the metyrapone test results. The control group had significantly higher cortisol responses than the AS and AD groups during LDAT. The control group had similar cortisol responses to the AS group but higher cortisol responses than the AD group during SDAT. The AS group was divided into 2 subgroups: AS patients with multiple pituitary hormone deficiencies (AS-multiple) and AS patients with idiopathic growth hormone deficiencies (AS-isolated). The AS-multiple group had statistically lower cortisol responses than the control group during LDAT. Receiver-operating characteristics analysis revealed that the cortisol cutoff value in LDAT was 19.8 microg/dl (100% sensitivity, 89% specificity) and 30.4 microg/dl in SDAT (82% sensitivity, 78% specificity). CONCLUSION: LDAT is capable of identifying patients with adrenal insufficiency more effectively than SDAT. The cortisol cutoff value in LDAT was calculated as 19.8 microg/dl with 100% sensitivity. AS patients with multiple pituitary hormone deficiencies had lower cortisol responses to LDAT than the control group implying that these patients might have a lower cortisol secretory capacity than healthy subjects.