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
60
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
60
fullerenes due to the potential blood contact. Currently, available data is not systematic and has not provided insights into possible side effects of C
60
fullerenes on blood components. In this study, water-soluble pristine C
60
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
60
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.
Post-COVID-19 conditions are the subject of extensive scientific study. It is known that system disorders may persist in people who recover from COVID-19 for 3 to 12 months (in most cases). The first ...line of systemic disorders is dysfunction of the immune system, especially the cytokine profile. The mechanism of the launch of immune complications is currently unknown. We hypothesized that anti-SARS-CoV-2 IgG might trigger the development of post-COVID-19 complications. Our research aimed to study the cytokine profile (including IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12β, TNF-α, IFN-γ) and the transcription factor NF-kB in the blood plasma of donor groups depending on various titers of anti-SARS-CoV-2 IgG. We determined the qualitative values of the cytokine parameters using ELISA (Enzyme Linked Immunosorbent Assay). We estimated the changes in the cytokine profiles in all donor groups. Differences between donor groups were established for each research parameter. We detected changes in NF-κB levels as a key transcription factor for the expression of inflammatory cytokines. The highest level was found in the donor group with a titer of anti-SARS-CoV-2 IgG 75 ± 5 Index (S/C). We detected some differences between donor groups in the levels of pro-inflammatory cytokines compared to a reference point. IL-1β, IL-6, IL-8, INF-γ, and TNF-α levels changed in most donor groups with titers of anti-SARS-CoV-2 IgG ≥ 10 ± 3 Index (S/C). In addition, we showed that the decrease in anti-inflammatory cytokine IL-4 in donor groups ranged from the titer of anti-SARS-CoV-2 IgG 55 ± 5 Index (S/C) to 85 ± 5 Index (S/C), but these changes for the anti-inflammatory cytokine IL-10 were not detected. We found that the cytokine profile may be affected during post-COVID-19 conditions. The cytokine profiles of the donor groups changed depending on the titers of anti-SARS-CoV-2 IgG. The obtained results testify to the fact that the antibody subpopulation may be a key reason for immune dysfunction, influencing the development of other pathological processes.
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.
Background: Vipera berus berus and Vipera berus nikolskii are the most widely spread Old World vipers in Europe, who contribute to almost all cases of snakebites on this territory. Their venoms are ...known to cause proteolysis, thrombocytopenia, induction of neurotoxicity and haemorrhage, among which proteolytic action constitute to the possible affection of all metabolic pathways in the targeted organs and in the whole organism. Methods: The influence of the viper venoms on the adrenal glands and testicles of injected rats was studied through the analysis of the concentration of proteins (Bradford method), evaluation of the qualitative protein profile (disc electrophoresis), distribution of active proteolytic molecules in the studied tissues (enzyme electrophoresis) and estimation of the appearance of low molecular weight molecules. Results: The decline of the number of the total protein, the alterations of the protein composition and the enzymatic redistribution were declared to appear in these organs under the action of the studied venoms proving the assumption of the proteolysis activation. Whereas, the increase in the level of low molecular weight molecules has emerged showing the onset of the state of toxicity. Conclusion: the study of the influence of the V. berus berus and V. berus nikolskii venoms on the protein balance of adrenal glands and testicles was performed, showing the impact on the amount of total proteins, its redistribution and connection with toxicity and proving the onset of pathological process.
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.
The accumulated data indicate that a high level of homocysteine may be a central pathogenetic factor of chronic obstructive pulmonary disease. In this study, we investigated the effect of ...hyperhomocysteinemia (HM) on protein homeostasis in the rat lungs. The level of proteins, peptides, total proteolytic activity, as well as protein-peptide composition, were evaluated. HM was induced by daily intragastric administration of DL-homocysteine thiolactone (100 mg·kg-1 of body weight) to albino non-linear male rats for 28 days. Twelve hours after the last administration, the rats were sacrificed and the lungs were harvested. Our findings showed that HM caused the disturbances in the protein homeostasis in the lungs that are manifested by a decrease in the level of proteins in the young and old animals and an increase in the level of peptides in the rats of all studied groups. We found a change in the protein composition in the lung of HM rats - a decrease in the level of proteins with a molecular weight of 50 kDa to 100 kDa simultaneously with an increase in the level of proteins with a molecular weight of less than 50 kDa. Despite the fact that the peptide profile was the same in both control animals and HM animals, the level of individual peptide fractions increased significantly in the rats with HM. Obtained data could contribute to explain, at least in part, the mechanisms involved in the pathogenesis of lung damage in HM.
Chronic pancreatitis (CP) is still a serious clinical problem due to the significant difficulties in its diagnosis, especially in the initial stages of development. Among the mechanisms that mediate ...the pathogenesis of CP and lead to pancreatitis-related disorders is unregulated activation of proteolytic enzymes, namely, matrix metalloproteinases (MMPs). The aim of our study was to determine the disturbances of protein metabolism under the conditions of CP alone or in combination with diabetes type 1 (CP+DT1). Herein, CP was induced in the nonlinear male rats by intraperitoneal injection of cerulein (5 µg·kg
of body weight; five times during fives day). DT1 was modeled in the rats with CP by a single intraperitoneal injection of streptozotocin (65 mg·kg
of the body weight). The levels of MMP-2 and -9 were determined by enzyme-linked immune sorbent assay, and the level of low and middle molecular weight (LMMW) substance was measured spectrophotometrically, while the peptide fractions were analyzed by size exclusion chromatography. The present study revealed a significant increase of MMP-2 and MMP-9 levels in the serum, liver and pancreas of the rats with CP and CP+DT1. Elevated levels of MMPS may act as a factor for the initiation of subsequent cascade of events resulting in the development of pancreatitis-associated complications. Pathogenesis of chronic pancreatitis alone or in combination with diabetes type 1 has been accompanied by the formation and accumulation of LMMW substance, changes in peptide composition and level of individual peptides in the tissues of the rats. Such alterations are among key triggers of amplification of metabolic disorders under chronic pancreatitis.
The aim of the present study was to evaluate the hypoglycemic activity of the aqueous extract from the fruit walls of
pods and to examine the potential mechanism underlying the improvement of the ...glycemic level. In the course of the study, diabetes mellitus was induced in rats with a single intraperitoneal injection of streptozotocin (45 mg·kg
b.w.). Diabetic and control rats were then orally administered with a single-dose or repeated-dose (28 day) of
extract (200 mg·kg
). Results show that the extract was found to possess significant hypoglycemic activity, and the study of glucose utilization by isolated rat hemidiaphragm suggests that the aqueous extract may enhance the peripheral utilization of glucose. The subsequent experiments have revealed that the
extract could increase glucose transporter 4 (GLUT-4) content in skeletal muscle cells of control and diabetic rats. Our data also indicate that the
extract did not affect the content of the insulin receptor, but significantly reduced the total tyrosine kinase activity in skeletal muscle cells of both experimental groups of rats. The present results clearly indicated that
extract may be beneficial for reducing hyperglycemia through its potency in regulation of glucose utilization via GLUT-4, but the current mechanism remains to be unidentified.
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