Redox State and Lysosomal Activity in Women with Ovarian Cancer with Tumor Recurrence and Multiorgan Metastasis

The aim of the study is to evaluate oxidant–antioxidant balance as well as lysosomal and anti-protease activities in ovarian cancer since it has been emphasized that the crucial inducing factor of carcinogenesis may be reactive oxygen/nitrogen species or, more precisely, oxidative stress-induced inflammation. The study involved 15 women with ovarian cancer, aged 59.9 ± 7.8 years, and 9 healthy women aged 56.3 ± 4.3 years (controls). The study material was venous blood collected from fasting subjects. In erythrocytes, the activities of superoxide dismutase, glutathione peroxidase, and catalase, as well as concentrations of conjugated dienes (CDs) and thiobarbituric acid reactive substances (TBARS), were investigated. CD, TBARS, and vitamins A and E plasma concentrations were also determined. Moreover, total antioxidant capacity and concentrations of 4-hydroxynonenal adducts and 8-iso-prostaglandin F2α, as well as activities of acid phosphatase, arylsulfatase, cathepsin D, and α1-antitrypsin, were studied in serum. The vitamin E and 8-iso-prostaglandin F2α concentrations as well as arylsulfatase activity were lower in the women with cancer compared to the controls (p = 0.006, p = 0.03, p = 0.001, respectively). In contrast, cathepsin D activity was lower in the controls (p = 0.04). In the peripheral blood of the women with cancer, oxidant–antioxidant and lysosomal disturbances were observed.

Insulin resistance is positively associated with plasma cathepsin D activity in NAFLD patients

Previous studies associated plasma cathepsin D (CTSD) activity with hepatic insulin resistance in overweight and obese humans. Insulin resistance is a major feature of non-alcoholic fatty liver disease (NAFLD) and is one of the multiple hits determining the progression towards non-alcoholic steatohepatitis (NASH). In line, we have previously demonstrated that plasma CTSD levels are increased in NASH patients. However, it is not known whether insulin resistance associates with plasma CTSD activity in NAFLD. To increase our understanding regarding the mechanisms by which insulin resistance mediates NAFLD, fifty-five liver biopsy or MRI-proven NAFLD patients (BMI>25kg/m2) were included to investigate the link between plasma CTSD activity to insulin resistance in NAFLD. We concluded that HOMA-IR and plasma insulin levels are independently associated with plasma CTSD activity in NAFLD patients (standardized coefficient β: 0.412, 95% Cl: 0.142~0.679, p=0.004 and standardized coefficient β: 0.495, 95% Cl: 0.236~0.758, p=0.000, respectively). Together with previous studies, these data suggest that insulin resistance may link to NAFLD via elevation of CTSD activity in plasma. As such, these data pave the way for testing CTSD inhibitors as a pharmacological treatment of NAFLD.

Lavandula Luisieri and Lavandula Viridis Essential Oils as Upcoming Anti-Protozoal Agents: A Key Focus on Leishmaniasis

Background and objectives: Leishmania species is the causative agent of leishmaniasis, a broad-spectrum clinical condition that can even be life-threatening when neglected. Current therapeutic strategies, despite beings highly cost-effective, have been increasingly associated with the appearance of drug-resistant microorganisms. Thus, an increasing number of thorough studies are needed towards upcoming drug discovery. This study aims to reveal the anti-protozoa activity of Lavandula luisieri and Lavandula viridis essential oils (EO) and their main components (1,8-cineole, linalool, and borneol). Materials and Methods: L. luisieri and L. viridis EO and their main components’ leishmanicidal effects were tested in vitro against Leishmania infantum, Leishmania major, and Leishmania tropica strains. Cell viability effects were estimated by using the tetrazolium-dye (MTT) colorimetric method, morphological changes were assessed by scanning electron microscopy (SEM) and ultrastructural investigation by transmission electronic microscopy (TEM). Phosphatidylserine externalization, mitochondrial membrane potential (MMP), and cathepsin D activity assessment were also carried out. Finally, cytotoxic activity of the studied matrices was also determined in mammalian cells. Results: Plant-studied EO exhibited prominent anti-Leishmania effects (IC50 = 31–263 µg/mL), with L. luisieri being the most active one. At concentrations corresponding to IC50 values, EO-exposed L. infantum promastigotes suffered marked ultrastructural modifications. The presence of aberrant-shaped cells, mitochondrial and kinetoplast swelling, and autophagosomal structures were the most common evidenced changes. L. luisieri EO exerted its leishmanicidal activity through different mechanisms, but mainly through unleashing apoptosis. Phosphatidylserine externalization, mitochondrial membrane potential loss, and cell-cycle arrest at G(0)/G(1) phase were the most remarkable apoptosis-mediated aspects. Inhibition of cathepsin D activity was also observed. No toxic effects were found on macrophage cells. Conclusions: L. luisieri seems to be an upcoming source of bioactive molecules for leishmaniasis control and to find leading molecules for new drugs formulation against Leishmania infections.

The Oxidant–Antioxidant Equilibrium and Inflammatory Process Indicators after an Exercise Test on the AlterG Antigravity Treadmill in Young Amateur Female Athletes

The AlterG antigravity treadmill allows running with a considerable weight reduction. Physical exercise practiced on this treadmill is an innovative method supporting the treatment of injuries in sports and rehabilitation of patients. The aim of the study was to investigate the effect of a 30 min run on the AlterG treadmill with 80% body weight reduction comparing the effect to the similar effort on the classic treadmill on the redox equilibrium and the activity of selected lysosomal enzymes and a serine protease inhibitor in the blood of amateur minor female volleyball players. Venous blood samples were taken before the exercise and 30 minutes and 24 hours after its completion. The obtained results were analysed using Tukey’s test and Pearson’s linear correlations were calculated. 24 h after the running test on classic treadmill, the erythrocytic superoxide dismutase activity was higher than before and 30 min after it, as well as compared to the run on AlterG treadmill (p<0.001). The erythrocytic-conjugated diene concentration 24 h after the exercise on the classic treadmill was meaningly higher compared to that after the exercise on the AlterG treadmill (p<0.001). The cathepsin D activity was significantly lower after the exercise in AlterG conditions compared to the baseline value and that measured after the exercise on classic treadmill (p<0.001). It seems that the exercise on the AlterG treadmill keeps the oxidant–antioxidant equilibrium and stabilizes lysosomal membranes in young, physically active women in contrast to the exercise on the classic treadmill. This trial is registered with CTRI/2018/01/011344.