ABSTRACT
Nowadays, more than two billion inhabitants of underdeveloped tropical and subtropical countries are at risk of being stung by scorpions. Scorpion stings annually cause 2000-3000 deaths as they can lead to the respiratory and/or cardiovascular complications. Pathogenesis of lung damage under scorpion envenomation is often comprehensive. Respiratory failure can have a cardiogenic origin, associated with venom neurotoxin action. However, some venom components can stimulate pro-inflammatory signaling cascades followed by cytokines synthesis, recruit and activate immune cells, participating in the inflammatory response in lung injury. Scorpions of the Leiurus genus ("deathstalker") are one of the most dangerous Arthropoda. To date, 22 species of this genus have been described, but the venom composition and the mechanisms of tissues damage under envenomation have been studied to some extent only for L. quinquestriatus, L. hebraeus, and L. abdullahbayrami. Scorpions of L. macroctenus species are expected to be very hazardous, but the possibility of their venom cause inflammation in the lung tissue has not been investigated to date. Therefore, in this study, we focused on evaluating the levels of cytokines and their regulators - transcription factors (HIF-1α and NF-κB) and growth factors (FGF-2, VEGF, and EGF) - in rat lung homogenates after L. macroctenus envenomation. The results revealed a decrease in the levels of most pro-inflammatory cytokines (IL-6, IL-8, IL-1ß and TNF-α) with simultaneous rise in the content of both anti-inflammatory cytokines (IL-4 and IL-10) and interferon-γ. Furthermore, the levels of all researched transcription factors and growth factors were shown to be increased too. The detected changes peak occurred at 24 h, whereas a tendency towards all indicators values normalization was observed in 72 h after venom injection. Thus, our results did not reveal signs of a classic inflammatory process in the lungs of rats injected with L. macroctenus venom. However, the obtained data indicate venom influence both on cytokine profile and on their regulators content in the rat lungs, which is a feature of certain alterations in the innate immune response, caused by studied venom components. But, the mechanisms of the changes we found require additional researches.
ABSTRACT
Background: Bladder cancer (BC) is an aggressive disease with a poor prognosis. A bladder tumor, like other malignant neoplasms, is characterized by the presence of both cancer cells and stromal cells which secrete cytokines, chemokines, growth factors, and proteolytic enzymes. One such class of proteolytic enzymes are serine proteases, which take part in the tumor microenvironment formation via supporting and contributing to tumor progression. This study aims to evaluate the proteolytic activity and serine protease contribution in plasma from BC patients. Methods: The research involved patients of Alexandrovsky city clinical hospital aged 52-76 with transitional cell carcinoma of the bladder. All examined patients were divided into five groups: the control group included conditionally healthy donors, while other patients were grouped according to their tumor stage (I, II, III and IV). Plasma plasminogen levels were determined by enzyme-linked immunosorbent assay, and the potential activity was measured by chromogenic plasminogen assay. Serine proteases fractions were obtained by the affinity chromatography method, and enzyme concentration in the selected fractions were determined by the Bradford method. Serine proteases distribution was investigated by electrophoresis in a polyacrylamide gel. Results: It was determined that the concentration, potential activity of plasminogen, and the total amount of serine proteases in plasma from BC patients were greater than the values of the corresponding indicators in healthy donors. This could be one of the factors contributing to increased proteolysis seen in the process of carcinogenesis. Plasminogen concentration in BC patients with stage IV disease; however, displayed a tendency to be reduced compared to earlier stages, and the potential activity of plasminogen was significantly lower in patients with stages III - IV BC. Futhermore, a tumor stage specific gradual decline in the serine protease plasma content was shown. The results of electrophoretic analysis established a significant diminishment in the percentage of high molecular weight components (under non-reducing conditions) and their complete disappearance (under reducing conditions) in plasma serine protease fractions from BC patients. A decline in the percentage of heavy and light plasmin chains in BC patients was also observed. Additionally, a rise in the degraded forms of plasminogen/plasmin content was seen in BC samples, as well as the presence of fractions corresponding to trypsin and NE (under non-reducing conditions) that were absent in the control samples. Conclusion: The results indicate significant changes in the proteolytic activity of plasma, from BC patients when compared to healthy controls, which is accompanied by alterations in serine protease distribution caused by tumor microenvironment pecularlities at the different stages of oncopathology.
ABSTRACT
AIM: To investigate the ability of collagen peptides derived from a jellyfish of the Antarctic region (Diplulmaris antarctica) to prevent the development of obesity in rats fed a high-calorie diet. METHODS: Collagen peptides were produced by pepsin hydrolysis of jellyfish-derived collagen. The purity of collagen and collagen peptides was confirmed by SDS-polyacrylamide gel electrophoresis. Rats were fed a high-calorie diet for ten weeks and were simultaneously orally administered collagen peptides (1 g per 1 kg of body weight every other day) starting from the fourth week. Body mass index (BMI), body weight gain, selected nutritional parameters, the key parameters associated with insulin resistance, and the level of oxidative stress markers were assessed. RESULTS: Compared with untreated obese rats, rats treated with hydrolyzed jellyfish collagen peptides had a decreased body weight gain and body mass index. They also had a decreased level of fasting blood glucose, glycated hemoglobin, insulin, lipid peroxidation products (conjugated dienes, Schiff bases), and oxidatively modified proteins, as well as a restored activity of superoxide dismutase. CONCLUSION: Collagen peptides obtained from Diplulmaris antarctica can be used to prevent and treat obesity caused by a high-calorie diet and pathologies associated with increased oxidative stress. Given the obtained results and the abundance of Diplulmaris antarctica in the Antarctic region, this species can be considered a sustainable source of collagen and its derivatives.
