Nazarii Kobyliak

Probiotics in prevention and treatment of obesity: a critical view.

The worldwide prevalence of obesity more than doubled between 1980 and 2014. The obesity pandemic is tightly linked to an increase in energy availability, sedentariness and greater control of ambient temperature that have paralleled the socioeconomic development of the past decades. The most frequent cause which leads to the obesity development is a dysbalance between energy intake and energy expenditure. The gut microbiota as an environmental factor which influence whole-body metabolism by affecting energy balance but also inflammation and gut barrier function, integrate peripheral and central food intake regulatory signals and thereby increase body weight. Probiotics have physiologic functions that contribute to the health of gut microbiota, can affect food intake and appetite, body weight and composition and metabolic functions through gastrointestinal pathways and modulation of the gut bacterial community.

Pathophysiological role of host microbiota in the development of obesity

Overweight and obesity increase the risk for a number of diseases, namely, cardiovascular diseases, type 2 diabetes, dyslipidemia, premature death, non-alcoholic fatty liver disease as well as different types of cancer. Approximately 1.7 billion people in the world suffer from being overweight, most notably in developed countries. Current research efforts have focused on host and environmental factors that may affect energy balance. It was hypothesized that a microbiota profile specific to an obese host with increased energy-yielding behavior may exist. Consequently, the gut microbiota is becoming of significant research interest in relation to obesity in an attempt to better understand the aetiology of obesity and to develop new methods of its prevention and treatment. Alteration of microbiota composition may stimulate development of obesity and other metabolic diseases via several mechanisms: increasing gut permeability with subsequent metabolic inflammation; increasing energy harvest from the diet; impairing short-chain fatty acids synthesis; and altering bile acids metabolism and FXR/TGR5 signaling. Prebiotics and probiotics have physiologic functions that contribute to the health of gut microbiota, maintenance of a healthy body weight and control of factors associated with obesity through their effects on mechanisms that control food intake, body weight, gut microbiota and inflammatory processes.

Insulin resistance and liver steatosis in chronic hepatitis C infection genotype 3

Hepatitis C virus (HCV) infection is a common chronic liver disease worldwide. Non-alcoholic fatty liver disease and insulin resistance (IR) are the major determinants of fibrosis progression and response to antiviral therapy. The pathogenetic link between IR and chronic HCV infection is complex, and is associated with HCV genotype. Liver steatosis is the most common in the patients infected with genotype 3 virus, possibly due to direct effects of genotype 3 viral proteins. To the contrary, hepatic steatosis in the patients infected with other genotypes is thought to be mostly due to the changes in host metabolism, involving IR. In HCV genotype 3, liver steatosis correlates with viral load, reverts after reaching the sustained virologic response and reoccurs in the relapsers. A therapeutic strategy to improve IR and liver steatosis and subsequently the response to antiviral treatment in these patients is warranted.

Short-term periodic consumption of multiprobiotic from childhood improves insulin sensitivity, prevents development of non-alcoholic fatty liver disease and adiposity in adult rats with glutamate-induced obesity

BackgroundToday the impairment of metabolism and obesity are being extensively investigated due to the significant increase of the prevalence of these diseases. There is scientific evidence that probiotics are beneficial for human health. Thus, the aim of the study was to investigate the effect of multiprobiotic “Symbiter acidophilic concentrated” on obesity parameters in the rats under experimental obesity.MethodsThe study was carried out on 60 newborn Wistar rats, divided into 3 groups, 20 animals in each (females – n = 10, males – n = 10): intact rats, monosodium glutamate (MSG-) and MSG + probiotic group. Rats of intact group were administered with saline (8 μl/g, subcutaneously (s.c.)). Newborns rats of MSG-group and MSG + probiotic group were injected with a solution of MSG (4.0 mg/g) s.c. at 2nd – 10th postnatal days. The MSG + probiotic group was treated with 140 mg/kg (1.4 × 1010 CFU/kg) of multiprobiotic “Symbiter”. MSG-group was treated with 2.5 ml/kg of water (per os) respectively. Administration was started at the age of 4 weeks just after wean and continued for 3 month intermittently alternating two-week course of introduction with two-week course of break.ResultsNeonatal treatment with MSG caused a stunted growth in both MSG-groups, which manifested with significantly smaller naso-anal length compared to adult intact rats. There was no significant difference in weight between intact and MSG-groups on 120th day. The adiponectin level in the serum of rats with MSG-induced obesity decreased by 2.43 times (p = 0.001) in males and 1.75 (p = 0.020) in females. Concentration of leptin in adipose tissue were significantly higher by 45.9% (p = 0.019) and 61.2% (p = 0.009) respectively in males and females compared to intact rats. Our study has indicated that daily oral administration of multiprobiotic to neonatal MSG-treated rats by 2-week courses led to significant reduce of total body and VAT weight with subsequent improvement in insulin sensitivity and prevention of non-alcoholic fatty liver (NAFLD) development.ConclusionsThese results have shown that periodic treatment with multiprobiotic prevents the MSG-induced obesity and NAFLD development.

Caffeine and cardiovascular diseases: critical review of current research

Abstract Caffeine is a most widely consumed physiological stimulant worldwide, which is consumed via natural sources, such as coffee and tea, and now marketed sources such as energy drinks and other dietary supplements. This wide use has led to concerns regarding the safety of caffeine and its proposed beneficial role in alertness, performance and energy expenditure and side effects in the cardiovascular system. The question remains “Which dose is safe?”, as the population does not appear to adhere to the strict guidelines listed on caffeine consumption. Studies in humans and animal models yield controversial results, which can be explained by population, type and dose of caffeine and low statistical power. This review will focus on comprehensive and critical review of the current literature and provide an avenue for further study.

The Role of Liver Biopsy to Assess Non-Alcoholic Fatty Liver Disease

Liver biopsy, since 1883, when were first performed, became the gold standard to confirm the earlier stages of fibrosis and grading of non-alcoholic fatty liver disease (NAFLD) and for distinguishing simple steatosis from non- alcoholic steatohepatitis (NASH). General limitations of liver biopsy are sampling error and inter- and intraobserver variability. Also procedure is invasive and thats why associated with some potential adverse effects and complications which may be minor (pain or vagal reactions, transient hypotension) or major such as visceral perforation, bile peritonitis or significant bleeding. Presence of steatosis, hepatocellular injury in the form of ballooning, lobular inflammation and perisinusoidal fibrosis, usually with a zone 3 distribution are considered to be most important histological features of adult NAFLD which may differ from bariatric surgery or pediatric patients. In addition, grading and staging and current semiquantitative systems for NAFLD assessment are discussed.

PREVENTION OF NAFLD DEVELOPMENT IN RATS WITH OBESITY VIA THE IMPROVEMENT OF PRO/ANTIOXIDANT STATE BY CERIUM DIOXIDE NANOPARTICLES

Background One of the pathogenic mechanisms of the nonalcoholic fatty liver disease (NAFLD) is the accumulation of reactive oxygen species, which in turn aggravates the disease progress. We have investigated novel cerium dioxide nanoparticles (nCeO2) due to their promising antioxidant auto-regenerative ability and low toxicity. Methods 30 white male Wistar rats were divided into 3 groups: control, monosodium glutamate (MSG)-induced obesity and MSG treated with nCeO2 (MSG+nCeO2) groups. Newborn rats of control group were injected with saline (control). MSG− and MSG+nCeO2 groups were injected with MSG (4 mg/g concentration, 8 μl/g volume) between the 2nd and the 10th days of life subcutaneously [13]. At the age of 1 month, rats of group II were administered water 2.9 ml/kg orally, MSG+nCeO2 group received 1 mM solution of nCeO2 1 mg/kg orally. 4-months rats were sacrificed and the liver was harvested for histological and biochemical analysis. To assess the morphological changes in the liver we used NAS (NAFLD activity score). The content of lipid peroxidation products and enzymatic activity of superoxide dismutase (SOD) and catalase in the liver were studied by standard biochemical methods [Refs]. Results In 4-month rats we found significantly lower total score (1.3±0.26 vs 3.6±0.34, p<0.001), degree of steatosis (1.1±0.18 vs 2.1±0.18, p<0.001), manifestation of lobular inflammation (0.2±0.13 vs 1.2±0.2, p<0.001) and ballooning degeneration (0.0±0.0 vs 0.3±0.15, p=0.034) due to NAS in the nCeO2 group compared to the MSG-group. nCeO2 significantly decreased lipid peroxidation in the liver tissue, namely it reduced the conjugated dienes content by 27% (p<0.05), TBA-products – by 43% (p<0.05) and Schiff bases – by 21% (p<0.05). Conclusions Due to its antioxidant properties nCeO2 significantly reduces the incidence of NASH and improves the main NAFLD histological features.

Perspectives and challenges of antioxidant therapy for atrial fibrillation

Atrial fibrillation (AF) is the most common sustained arrhythmia associated with significant morbidity and mortality. The mechanisms underlying the pathogenesis of AF are poorly understood, although electrophysiological remodeling has been described as an important initiating step. There is growing evidence that oxidative stress is involved in the pathogenesis of AF. Many known triggers of oxidative stress, such as age, diabetes, smoking, and inflammation, are linked with an increased risk of arrhythmia. Numerous preclinical studies and clinical trials reported the importance of antioxidant therapy in the prevention of AF, using vitamins C and E, polyunsaturated fatty acids, statins, or nitric oxide donors. The aim of our work is to give a current overview and analysis of opportunities, challenges, and benefits of antioxidant therapy in AF.

Immunomodulatory effects of stem cells: Therapeutic option for neurodegenerative disorders

Stem cells have the capability of self-renewal and can differentiate into different cell types that might be used in regenerative medicine. Neurodegenerative diseases such as Alzheimers disease (AD), Parkinsons disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) currently lack effective treatments. Although stem cell therapy is still on the way from bench to bedside, we consider that it might provide new hope for patients suffering with neurodegenerative diseases. In this article, we will give an overview of recent studies on the potential therapeutic use of mesenchymal stem cells (MSCs), neural stem cells (NSCs), embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and perinatal stem cells to neurodegenerative disorders and we will describe their immunomodulatory mechanisms of action in specific therapeutic modalities.

Cerium dioxide nanoparticles possess anti-inflammatory properties in the conditions of the obesity-associated NAFLD in rats

BACKGROUND Obesity is a risk factor for non-alcoholic fatty liver disease (NAFLD). The disease is associated with impairment of pro/antioxidant equilibrium and the inflammation in liver tissue. The aim of the work was to investigate the anti-inflammatory properties of the nanocrystalline cerium dioxide (nCeO2) on the rat model of NAFLD associated with monosodium glutamate (MSG)-induced obesity. METHODS The study was carried out on three groups of rats: control, MSG- and MSG+nCeO2. They were injected with saline (control) or MSG. A month after born MSG-rats had been treated with water in a volume of 2.9ml/kg, MSG+CeO2 groups - with CeO2 intragastrically (i.g.). The anthropometric and carbohydrate metabolism parameters, content of proinflammatory cytokines (interleukin (IL)-1β, IL-12Bp40, interferon-γ (INF-γ)) and anti-inflammatory cytokines (IL-4, IL-10, tumor growth factor-β (TGF-β)) were measured by ELISA. RESULTS We have demonstrated the anti-obesity effect of nanocrystalline cerium dioxide and for the first time its anti-inflammatory properties. Nanoparticles reduced the content of pro-inflammatory cytokines (IL-1β, IL-12Bp40) in rat serum and restored the level of anti-inflammatory cytokines (IL-4, IL-10, TGF-β) to the control values. CONCLUSION The precise mechanisms of this phenomenon remain to be unclear but we suppose they are at least partially associated with the strong anti-oxidant action of studied substance. Nanocrystalline cerium dioxide attenuates the inflammatory processes in rat blood that can prevent obesity complications and liver injury.