The effect of marathon on mRNA expression of anti-apoptotic and pro-apoptotic proteins and sirtuins family in male recreational long-distance runners

<p>Abstract</p> <p>Background</p> <p>A large body of evidence shows that a single bout of strenuous exercise induces oxidative stress in circulating human lymphocytes leading to lipid peroxidation, DNA damage, mitochondrial perturbations, and protein oxidation.</p> <p>In our research, we investigated the effect of physical load on the extent of apoptosis in primary cells derived from blood samples of sixteen healthy amateur runners after marathon (a.m.).</p> <p>Results</p> <p>Blood samples were collected from ten healthy amateur runners peripheral blood mononuclear cells (PBMCs) were isolated from whole blood and bcl-2, bax, heat shock protein (HSP)70, Cu-Zn superoxide dismutase (SOD), Mn-SOD, inducible nitric oxide synthase (i-NOS), SIRT1, SIRT3 and SIRT4 (Sirtuins) RNA levels were determined by Northern Blot analysis. Strenuous physical load significantly increased HSP70, HSP32, Mn-SOD, Cu-Zn SOD, iNOS, GADD45, bcl-2, forkhead box O (FOXO3A) and SIRT1 expression after the marathon, while decreasing bax, SIRT3 and SIRT4 expression (P < 0.0001).</p> <p>Conclusion</p> <p>These data suggest that the physiological load imposed in amateur runners during marathon attenuates the extent of apoptosis and may interfere with sirtuin expression.</p

Evidences of a New Psychobiotic Formulation on Body Composition and Anxiety

Background. Gut microbiota is implied in obesity, because of its ability to harvest energy from diet, and in the regulation of behavior. Given the link between gut microbiota, body composition, obesity, and anxiety, the aim of this study was to evaluate the effects of a new psychobiotic formulation. Methods. Eligible patients were randomly divided into three groups: psychobiotics oral suspension group (POSG); dietary treatment group (DTG); combined treatment group (CTG). All subjects underwent body composition and psychological profile evaluation. Results. Significant changes in body composition parameters in each group were relieved after all treatments. Hamilton anxiety rating scale (HAM-A) highlighted a significant reduction of the total score for all study population after treatments in POSG (p=0.01) and CTG (p=0.04). A reduction of HAM-A total score in anxious subjects in POSG or CTG and a significant reduction of positive subjects for HAM-A in POSG (p=0.03) and in CDG (p=0.01) were shown. Discussion. Three-week intake of selected POS represents a good approach to solve problems related to obesity and behavior disorders. However, new clinical trials need to be performed on a larger population and for a longer period of treatment before definitive conclusions can be made. This trial is registered with NCT01890070

PYRROLO[1,2-b][1,2,5]BENZOTHIADIAZEPINES (PBTDs) induce apoptosis in K562 cells

BACKGROUND: The objective of this study was to gain insight into the molecular mechanism of induced cell death (apoptosis) by PYRROLO [1,2-b][1,2,5]BENZOTHIADIAZEPINES (PBTDs) series compounds, using human (K562) cells as a model. METHODS: We focused our attention on some members of the PBTDs family to test their potential apoptotic activity in K562 cells. Important apoptotic activity was demonstrated, as evidenced by the concentration and percentage of cell death quantified by measuring PI-uptake by flow cytometry, and DNA fragmentation analyzed by agarose gel electrophoresis, generating a characteristic ladder pattern of discontinuous DNA fragments. The expression of Bcl-2 family was tested using western blotting and transfection method. RESULTS: PBTDs-mediated suppression of K562 cell proliferation was induced by apoptosis characterized by the appearance of DNA fragmentation and was associated with the poly(ADP-ribose)polymerase (PARP) cleavage. PBTD-1 and -3 treatment resulted in caspase-3 activation through down-regulation of Bcl-2 and up-regulation of Bax. Furthermore, we used K562/vector and K562/bcl-2 cells, which were generated by transfection of the cDNA of the Bcl-2 gene. As compared with K562/vector, K562/Bcl-2 cells exhibited a 4-fold greater expression of Bcl-2. Treatment with 10 muM PBTD-1 and -3 for 24 h produced morphological features of apoptosis and DNA fragmentation in K562/vector cells, respectively. In contrast, PBTD-1 and -3-induced caspase-3 activation and apoptosis were inhibited in K562/Bcl-2. Furthermore, Bcl-2 overexpressing cells exhibited less cytocrome c release during PBTDs-induced apoptosis. CONCLUSION: These results indicate that PBTDs effectively induce apoptosis of K562 leukemia cells through the activation of caspase cascades. In addition, these findings indicate that Bcl-2 inhibits PBTD-1 and -3 induced-apoptosis via a mechanism that interferes with cytocrome c release, and the activity of caspase-3, which is involved in the execution of apoptosis

Dietary Vitamin E as a Protective Factor for Parkinson's Disease: Clinical and Experimental Evidence

Effective disease-modifying treatments are an urgent need for Parkinson's disease (PD). A putative successful strategy is to counteract oxidative stress, not only with synthetic compounds, but also with natural agents or dietary choices. Vitamin E, in particular, is a powerful antioxidant, commonly found in vegetables and other components of the diet. In this work, we performed a questionnaire based case-control study on 100 PD patients and 100 healthy controls. The analysis showed that a higher dietary intake of Vitamin E was inversely associated with PD occurrence independently from age and gender (OR = 1.022; 95% CI = 0.999–1.045; p &lt; 0.05), though unrelated to clinical severity. Then, in order to provide a mechanistic explanation for such observation, we tested the effects of Vitamin E and other alimentary antioxidants in vitro, by utilizing the homozygous PTEN-induced kinase 1 knockout (PINK1−/−) mouse model of PD. PINK1−/− mice exhibit peculiar alterations of synaptic plasticity at corticostriatal synapses, consisting in the loss of both long-term potentiation (LTP) and long-term depression (LTD), in the absence of overt neurodegeneration. Chronic administration of Vitamin E (alpha-tocopherol and the water-soluble analog trolox) fully restored corticostriatal synaptic plasticity in PINK1−/− mice, suggestive of a specific protective action. Vitamin E might indeed compensate PINK1 haploinsufficiency and mitochondrial impairment, reverting some central steps of the pathogenic process. Altogether, both clinical and experimental findings suggest that Vitamin E could be a potential, useful agent for PD patients. These data, although preliminary, may encourage future confirmatory trials

Influence of FTO rs9939609 and Mediterranean diet on body composition and weight loss: a randomized clinical trial

Background The Mediterranean diet (MeD) plays a key role in the prevention of obesity. Among the genes involved in obesity, the Fat mass and obesity-associated gene (FTO) is one of the most known, but its interaction with MeD remained uncertain so far. Methods We carried out a study on a sample of 188 Italian subjects, analyzing their FTO rs9939609 alleles, and the difference in body composition between the baseline and a 4-weeks nutritional intervention. The sample was divided into two groups: the control group of 49 subjects, and the MeD group of 139 subjects. Results We found significant relations between MeD and both variation of total body fat (ΔTBFat) (p = 0.00) and gynoid body fat (p = 0.04). ∆TBFat (kg) demonstrated to have a significant relation with the interaction diet-gene (p = 0.04), whereas FTO was associated with the variation of total body water (p = 0.02). Conclusions MeD demonstrated to be a good nutritional treatment to reduce the body fat mass, whereas data about FTO remain uncertain. Confirming or rejecting the hypothesis of FTO and its influence on body tissues during nutritional treatments is fundamental to decide whether its effect has to be taken into consideration during both development of dietetic plans and patients monitoring. Trial Registration ClinicalTrials.gov Id: NCT01890070. Registered 01 July 2013, https://clinicaltrials.gov/ct2/show/NCT0189007

Involvement of the membrane-bound Na,K ATPase in the evolution of experimental injuries of the spinal cord.

[No abstract available

Antiapoptotic activity of bovine herpesvirus type-1 (BHV-1) UL14 protein

Viruses have evolved different strategies to interfere with apoptotic pathways in order to halt cellular responses to infection. One previous study showed that transient transfection of bovine herpesvirus type-1 (BHV-1) UL14 protein is efficient in protecting Madin Darby kidney (MDBK) and human chronic myelogenous leukemia (K562) cells from sorbitol-induced apoptosis. This protein corresponds to a putative protein of BHV-1, which shares aminoacid sequence with a part of the peptide-binding domain conserved in human heat shock protein (HSP70) family. The pBK-CMV-UL14 plasmid transfected MDBK cells treated with sorbitol did not show caspase-3 and caspase-9 activation with respect to non-transfected MDBK cells (UL14 negative). Furthermore, we report that the expression of the full length sequence of BHV-1 UL14 is evident after 7 h of infection of BHV-1 on MDBK cells which were then treated with sorbitol. These results indicate that UL14 gene product has important implications to enhance cell survival in response to apoptotic stimuli