Relationship between Hypoxia and Hypercapnia Tolerance and Life Expectancy.

The review discusses the potential relationship between hypoxia resistance and longevity, the influence of carbon dioxide on the mechanisms of aging of the mammalian organism, and intermittent hypercapnic-hypoxic effects on the signaling pathways of aging mechanisms. In the article, we focused on the potential mechanisms of the gero-protective efficacy of carbon dioxide when combined with hypoxia. The review summarizes the possible influence of intermittent hypoxia and hypercapnia on aging processes in the nervous system. We considered the perspective variants of the application of hypercapnic-hypoxic influences for achieving active longevity and the prospects for the possibilities of developing hypercapnic-hypoxic training methods.

Unraveling the Mechanism of Platelet Aggregation Suppression by Monoterpenoids.

Platelet aggregation causes various diseases and therefore challenges the development of novel antiaggregatory drugs. In this study, we report the possible mechanism of platelet aggregation suppression by newly synthesized myrtenol-derived monoterpenoids carrying different heteroatoms (sulphur, oxygen, or nitrogen). Despite all tested compounds suppressed the platelet aggregation in vitro, the most significant effect was observed for the S-containing compounds. The molecular docking confirmed the putative interaction of all tested compounds with the platelet's P2Y12 receptor suggesting that the anti-aggregation properties of monoterpenoids are implemented by blocking the P2Y12 function. The calculated binding force depended on heteroatom in monoterpenoids and significantly decreased with the exchanging of the sulphur atom with oxygen or nitrogen. On the other hand, in NMR studies on dodecyl phosphocholine (DPC) as a membrane model, only S-containing compound was found to be bound with DPC micelles surface. Meanwhile, no stable complexes between DPC micelles with either O- or N-containing compounds were observed. The binding of S-containing compound with cellular membrane reinforces the mechanical properties of the latter, thereby preventing its destabilization and subsequent clot formation on the phospholipid surface. Taken together, our data demonstrate that S-containing myrtenol-derived monoterpenoid suppresses the platelet aggregation in vitro via both membrane stabilization and blocking the P2Y12 receptor and, thus, appears as a promising agent for hemostasis control.

The relationship between oxidative stress and cytogenetic abnormalities in B-cell chronic lymphocytic leukemia.

BACKGROUND: Prospective data on the value of oxidative stress in the pathogenesis of B-CLL are limited, and data on the relationship between oxidative stress and the presence of cytogenetic abnormalities (CA) in this pathology are almost absent. In the present study, we evaluated the serum levels of oxidative stress biomarkers [conjugated dienes (CD), malondialdehyde (MDA), and nitrite levels] and antioxidant biomarkers [ceruloplasmin (CP) level and glutathione peroxidase (GPx) activity] in B-CLL and investigated the relationship between these biomarkers and the presence of CA. MATERIAL AND METHODS: A total of 64 B-CLL patients were grouped with respect to the Rai stages of the disease, then to the mutated/unmutated status of IGHV genes as well as to the presence/absence of CA. The type and frequency of CA in the B-CLL cells were determined by fluorescence in situ hybridization. Control group included 30 healthy volunteers. The CD, MDA, and nitrite levels as well as the GPx activity were evaluated spectrophotometrically; the CP level was evaluated turbidimetrically. RESULTS: Compared to control, the B-CLL patients had increased CD, MDA, and nitrite levels as well as increased CP level and decreased GPx activity, which was observed at all Rai stages of the disease. CA were identified in 47 patients: del(13q14.3) as a single CA occurred in 18 patients, del(11q22.3) in 5 patients, del(17p13.1) in 4 patients, tri 12 in 5 patients, and multiple CA occurred in 15 patients. Compared to patients without CA, isolated del(17p13.1) was associated with higher CD and MDA levels while multiple CA with elevated CD levels only. The nitrite and CP levels and the activity of GPx in patients with CA were close to those in patients with normal FISH. The odds of harboring CA increased by a factor of 1.88 (p = 0.004) for every one unit increase in serum CD level (µmol/L), as assessed by binomial logistic regression. CONCLUSION: The results indicate that B-CLL patients experience increased oxidative stress and the relative deficiency of the antioxidant defense system. Increased CD level was independently associated with greater likelihood of harboring CA.