Despite clearly recognized links between increased body mass and increased risk for various pathological conditions, therapeutic options to treat obesity are still very limited. The aim of the ...present study is to explore the effect of low-molecular-mass collagen fragments obtained from the scales of Antarctic wild marine fish on rats' visceral and subcutaneous white adipose tissue in a high-calorie diet-induced obesity model.
The study was conducted on outbred rats, which were divided into 3 experimental groups: (
) control, consuming standard food (3.81 kcal/g), (
) obese group, consuming a high-calorie diet (5.35 kcal/g), and (
) obese group, consuming a high-calorie diet (5.35 kcal/g) with intragastric administration of low-molecular-mass collagen fragments (at a dose 1 g/kg of body mass during 6 weeks). Low-molecular-mass collagen fragments were obtained by a procedure that included collagen extraction from fish scales and enzymatic hydrolysis with pepsin. Apart from hematoxylin and eosin staining, fibrosis level was assessed by histochemical Van Gieson's trichrome picrofuchsin staining, and mast cells were analysed by toluidine blue O staining.
Group treated with low-molecular-mass fragments of collagen exhibited decreased rate of mass gain, relative mass, area occupied by collagen fibre of both visceral and subcutaneous adipose tissue, and cross-sectional area of both visceral and subcutaneous adipocytes. Treatment with low-molecular-mass fragments of collagen reduced the infiltration of immune cells, number of mast cells and their redistribution back to the septa. This was also accompanied by a decreased number of the crown-like structures formed by the immune cells, which are markers of chronic inflammation that accompanies obesity.
This is the first study that reports the anti-obesity effect of low-molecular-mass fragments produced as a result of controlled hydrolysis of collagen from the scales of Antarctic wild marine fish in the
model. Another novelty of this work is the observation that the tested collagen fragments not only reduce the body mass, but also improve the morphological and inflammatory parameters (decrease in the number of crown-like structures, immune cell infiltration, fibrosis and mast cells). Altogether, our work suggests that low-molecular-mass collagen fragments are a promising candidate for amelioration of some comorbidities linked to obesity.
C
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fullerenes have proved their therapeutic effects and efficacy by the results of countless experiments. For further usage of these nanoparticles, the systematic toxicological investigations are ...required. Blood compatibility should be studied for C
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fullerenes due to the potential blood contact. Currently, available data is not systematic and has not provided insights into possible side effects of C
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fullerenes on blood components. In this study, water-soluble pristine C
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fullerenes were tested in vitro to assess their biocompatibility in rabbit. The blood compatibility has been evaluated looking at the impact of C
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fullerenes on erythrocyte integrity, platelet aggregation, and some blood factors involved in coagulation. Our results revealed that C
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fullerenes cannot elicit hemolysis at studied concentrations and did not show any effect on coagulation process. C
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fullerenes in concentration-dependent manner increased ADP-dependent platelet aggregation and changed the key kinetic parameters of these processes. C
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fullerenes inhibited thrombin amidolytic activity but did not affect the activities of other studied coagulation factors. The prothrombotic property of C
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fullerenes could be the potential risk factor that leads to enhancement of vascular thrombosis. The ability of fullerene to inhibit thrombin activity is important for the pharmacological use of these carbon nanoparticles as anticoagulant agents.
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-1β 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.
•L. macroctenus envenomation cause decrease in the levels of most pro-inflammatory cytokines.•Levels of transcription factors and growth factors increase after L. macroctenus envenomation.•L. macroctenus venom rise the content of anti-inflammatory cytokines and interferon-γ.•Peak of changes occurred at 24 h after L. macroctenus venom injection.•Components of the venom of the scorpion L. macroctenus activate the innate immune response.
Aim: To investigate the serotonin and von Willebrand factor (vWF) concentrations among unstable angina (UA) patients without and with progression toward myocardial infarction (outcome) and to assess ...the utility of both as prognostic markers of UA complications.
Materials and methods: In observational cohort study, we recruited 103 patients with ischemic heart disease (the median age 65.0 (59.0-69.0) years, 45 females (43.7%)). After full set of investigations including high sensitive Troponin I test and 28-day follow-up period, we defined three groups: Group 1 - stable angina patients (n=22) as control, Group 2 - UA patients without outcome (n=71), Group 3 - UA patients with outcome (n=10). We analyzed the blood plasma serotonin content by the ion-exchange chromatography with measurement of serotonin on fluorescence spectrophotometer. VWF concentration was determined by ELISA. We compared the concentrations of observed parameters among the groups with the Kruskal-Wallis test (with post-hoc Mann-Whitney test with Bonferroni-Holm correction). We assessed binary logistic models, receiver operating characteristic curves, calculated sensitivity (Se), specificity (Sp), and positive likelihood ratio (LR+) for each indicator.
Results: We registered elevation in serotonin concentration and decline in vWF concentration in Group 3 in comparison with Group 2 (22.670 (20.687-24.927) μg/ml vs 11.980 (8.120-15.000) μg/ml, p< 0.001, and 0.117 (0.109-0.120) rel.units/ml vs 0.134 (0.127-0.143) rel.units/ml, p < 0.001) and Group 1 (12.340 (10.052-13.619) μg/ml, p < 0.001, and 0.137 (0.127-0.156) rel.units/ml, p < 0.001), respectively. No significant differences in serotonin and vWF concentrations between Group 1 and Group 2 were detected (p=0.81 and p=0.36, respectively). The probability of outcome increased significantly (by 60.7% and 59.7%, LR+ 19.0 6.0, 60.0 and 18.0 3.9, 80.0) if serotonin concentration was above 21.575 μg/ml (Se=80.0%, Sp=95.8%, AUC=0.975) and vWF concentration was below 0.114 rel.units/ml (Se=50.0%, Sp=97.2%, AUC=0.973), respectively.
Conclusions: Serotonin and vWF as biomarkers are demonstrated promising results for rule-in the patients with risk of short-term UA progression toward myocardial infarction.
Ulcers and slow wound healing are common in diabetic polyneuropathy (DP), as well as shooting or burning pain, sensitivity to touch or lack of sensitivity, low oxygenation of nerve tissue, ...conductivity disorders and various vascular disorders. The mechanisms of DP development are complex and have not been completely studied. To take into account the role of B group vitamins, we investigated histological structure of nerve tissue, the level of different growth factors and the qualitative composition of active proteolytic enzymes in rats with DP and after the use of the metabolic drug Cocarnit for 9 days. This drug composition include nicotinamide, cocarboxylase, cyanocobalamin, adenosine triphosphate disodium trihydrate. We used an histological study of sciatic nerve; enzyme-linked immunosorbent assay and enzyme electrophoresis methods. In rats with DP, fragmentation of nerve tissue and their necrosis was established. Moreover, degraded forms of plasmin that has a fully functional serine proteinase domain are evident, and, therefore, it exhibits proteolytic properties. DP led to a decrease of neuron growth factor (NGF), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). After treatment, the histological structure of nerve tissue was significantly improved, and the expression of growth factors NGF and bFGF was increased. Our study demonstrated that administration of Corcarnit brought about the complete restoration of the activation potential of plasmin and the almost disappearance of all degraded forms which were evident in the group with DP.
Bladder cancer (BC) is a worldwide common disease with a high mortality rate. Recognizing the dynamic changes in plasma that proteases and their inhibitors undergo might be valuable in understanding ...the carcinogenesis of invasive bladder cancer and in identifying BC patients with poor prognosis. This study aims to determine the activity of the proteolytic enzyme system and their inhibitors in patients with BC. In this paper, the total proteolytic activity, the activity of matrix metalloproteases (MMPs) and serine proteases was analyzed by the method of caseinolytic activity. For detection of activity of some inhibitors of proteolysis, we used the unified method for determining the activity of alpha-1-antitrypsin (α1A) and alpha-2-Macroglobulin (α2M) in human plasma. The level of medium-mass molecules (MMM) was assessed spectrophotometrically by applying the Nikolaichik method.
The activity of MMPs was elevated in all groups of patients. Moreover, the activity of serine proteases was found to be enhanced in patients with Stage I, III and IV BC, while the activity of α1A was up by 1.4 and 1.3 times in patients with Stage I and Stage IV. The most significant increase was observed with regard to the activity of α2M in patients with I and III stages of BC. In addition, the level of MMM correlated with cancer stage. Indeed, the highest increase in the activity of protease inhibitors was observed in Stage I bladder cancer patients, which might signify their protective role at the onset of the bladder carcinogenesis. In contrast, significant growth in activity of α2M in patients with III stage of BC may point at a compensatory mechanism that inhibits tumor growth.
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