Introduction. Liraglutide (L) is the analogue of human glucagon-like peptide 1 which stimulates glucose-dependent insulin secretion and can modify the level of inflammatory biomarkers. L can influence NF-kB inflammatory cascade, but the mechanisms of anti-inflammatory activities of L remain to be determined. In animal models L influenced an activity of Sirtuin 1(SIRT1). Moreover, recent evidences strongly suggest that SIRT1 up-regulation may serve as a potent therapeutic approach against development and progression of diabetic complications. The aim of this study was to investigate L effects directed on the pro-inflammatory NF-kB pathway and expression of SIRT1 in obese patients with type 2 diabetes mellitus (DM). Materials and Methods. 15 obese patients with type 2 diabetes were studied, all using metformin (1-2 g/day) and sulfonylurea (glimiperide). All patients received L 1.2 mg daily add-on to stable therapy for 6 weeks. Blood samples were collected before, 6 weeks after start of treatment and after an overnight fast 6 weeks after stopping L, mononuclear cells (MNC) were isolated. The mRNA expressions of TNF-α, TLR2, TLR4, NOD1, IL-2 and SIRT1 were measured in MNC by RT-PCR. Ceruloplasmin concentration was measured in plasma by photometric method. Results. In this add-on pilot clinical investigation we received new data that L can inhibit proinflammatory NF-kB pathway by increased SIRT1 expression in obese patients with type 2 DM improving metabolic profile. The mRNA expression in MNC of TNF-α, IkB, TLR2, TLR4, and plasma ceruloplasmin fell after 6 weeks of L. Expressions of IL-2 and NOD-1 were stable. There was a significant increase of SIRT1 mRNA expression. The mRNA expression in MNC of TNF-α, IkB, TLR2, TLR4, NOD1, SIRT1 and ceruloplasmin concentrations did not reverse to baseline levels after 6 weeks stopping of L treatment. IL-2 expression decreased in comparison with basic level. Conclusions. L has a potent anti-inflammatory effect as do GLP-1 agonists due to inhibition of NF-kB pathways and up-regulate SIRT1 expression, down-regulating pro-inflammatory factors including cytokines (TNF-α), extra- and intracellular receptors (TLR2, TLR4), and inflammation markers such as ceruloplasmin. Long lasting effects of L can be mediated by epigenetic regulation of NF-kB pathway by SIRT-1.

Introduction. The master clock, which is located in the suprachiasmatic nucleus (SCN), harmonizes clock genes present in the liver to synchronize life rhythms and bioactivity with the surrounding environment. The reversed feeding disrupts the expression of clock genes in the liver. Recently, a novel role of PPAR-γ as a regulator in correlating circadian rhythm and metabolism was demonstrated. This study examined the influence of PPAR-γ agonist pioglitazone (PG) on the mRNA expression profile of principle clock genes and inflammation-related genes in the mouse liver disrupted by reverse feeding. Methods. Mice were randomly assigned to daytime-feeding and nighttime-feeding groups. Mice in daytime-feeding groups received food from 7 AM to 7 PM, and mice in nighttime-feeding groups received food from 7 PM to 7 AM. PG was administered in the dose of 20 mg/kg per os as aqueous suspension 40 μl at 7 AM or 7 PM. Each group consisted of 12 animals. On day 8 of the feeding intervention, mice were sacrificed by cervical dislocation at noon (05 hours after light onset (HALO)) and midnight (HALO 17). Liver expressions of Bmal1, Clock, Rev-erb alpha, Cry1, Cry2, Per1, Per2, Cxcl5, Nrf2, and Ppar-γ were determined by quantitative reverse transcription PCR. Liver expression of PPAR-γ, pNF-κB, and IL-6 was determined by Western blotting. Glucose, ceruloplasmin, total cholesterol, triglyceride concentrations, and ALT and AST activities were measured in sera by photometric methods. The null hypothesis tested was that PG and the time of its administration have no influence on the clock gene expression impaired by reverse feeding. Results. Administration of PG at 7 AM to nighttime-feeding mice did not reveal any influence on the expression of the clock or inflammation-related genes either at midnight or at noon. In the daytime-feeding group, PG intake at 7 PM led to an increase in Per2 and Rev-erb alpha mRNA at noon, an increase in Ppar-γ mRNA at midnight, and a decrease in Nfκb (p65) mRNA at noon. In general, PG administration at 7 PM slightly normalized the impaired expression of clock genes and increased anti-inflammatory potency impaired by reversed feeding. This pattern was supported by biochemical substrate levels—glucose, total cholesterol, ALT, and AST activities. The decrease in NF-κB led to the inhibition of serum ceruloplasmin levels as well as IL-6 in liver tissue. According to our data, PG intake at 7 PM exerts strong normalization of clock gene expression with a further increase in Nrf2 and, especially, Ppar-γ and PPAR-γ expression with inhibition of Nfκb and pNF-κB expression in daytime-feeding mice. These expression changes resulted in decreased hyperglycemia, hypercholesterolemia, ALT, and AST activities. Thus, PG had a potent chronopharmacological effect when administered at 7 PM to daytime-feeding mice. Conclusions. Our study indicates that reversed feeding induced the disruption of mouse liver circadian expression pattern of clock genes accompanied by increasing Nfκb and pNF-κB and IL-6 expression and decreasing Nrf2 and PPAR-γ. Administration of PG restored the clock gene expression profile and decreased Nfκb, pNF-κB, and IL-6, as well as increased Nrf2, Ppar-γ, and PPAR-γ expression. PG intake at 7 PM was more effective than at 7 AM in reversed feeding mice.

SARS-CoV-2 is a global threat that influenced healthcare systems around the world. This virus caused an infection in humans with different clinical signs and syndromes, severity, and mortality. The key components of the COVID-19 molecular pathogenesis are coronavirus entry and replication, antigen presentation, humoral and cellular immunity, cytokine storm, coronavirus immune evasion. The analysis of recent literature displayed possible molecular targets in the key components of the COVID-19 pathogenesis. Some of these targets might have gene polymorphisms that influenced the COVID-19 course. Unfortunately, several findings are still putative or extrapolated from SARS and MERS experimental investigations or clinical trials. We systematised original data about gene polymorphisms of possible molecular targets and associations with the COVID-19 course. Most data were obtained for angiotensin-converting enzymes 1 and 2, TMPRSS2 gene polymorphisms. Only a few results were found for gene polymorphisms of adhesion molecules, interferon system components, cytokines, and transcriptional factors, oxidative stress and metabolic molecules, as well as haemocoagulation. Understanding the host gene variability and its associations with COVID-19 can provide insights into the disease pathogenesis, individual susceptibility to SARS-CoV-2 infection, severity, complications, and mortality prognosis for the disease. Besides, these data might help in the identification of appropriate targets for intervention.

Introduction The severity of SARS-CoV-2 induced coronavirus disease 19 (COVID-19) depends on the presence of risk factors and the hosts' gene variability. There are preliminary results that gene polymorphisms of the renin-angiotensin system can influence the susceptibility to and mortality from COVID-19. Angiotensin II type 1 receptor (AT1R) might be a gene candidate that exerts such influence. The aim of this study was to elaborate on the association between A1166C at1r polymorphic variants and the susceptibility to and severity of COVID-19 in the Ukrainian population. Methods The study population consisted of the Ukrainian population (Poltava region) with COVID-19, divided into three clinical groups in accordance with oxygen requirement: patients without oxygen therapy ( n = 110), with non-invasive ( n = 136) and invasive ( n = 36) oxygen therapy. The A1166C polymorphism of the at1r was determined by polymerase chain reaction with subsequent restrictase analysis. In an attempt to better explain the role of the A1166C at1r polymorphism we compared its association with COVID-19, essential hypertension ( n = 79), renoparenchimal hypertension ( n = 30) and dyscirculatory encephalopathy ( n = 112). The data for this comparison were obtained by meta-analysis. Results We observed significant differences in the frequency of AA, AC and CC genotypes in the groups of COVID-19 patients with non-invasive and invasive oxygen therapy in comparison with control subjects as well as in the frequency of combined AC + CC genotype between the groups of COVID-19 patients with any types of oxygen therapy and patients without oxygen therapy. The frequency of the 1166C allele was higher in COVID-19 patients with invasive oxygen therapy (OR = 2.06; CI (1.20–3.53); p = 0.013). We obtained important results indicating that there were no differences between the frequency of at1r polymorphisms in patients with cardiovascular disease and severe COVID-19 with invasive oxygen therapy as well as those who died due to COVID-19. Conclusion Our study indicated the presence of an association between the A1166C at1r polymorphisms and the severity of COVID-19 in the Ukrainian population. It seems that in carriers of 1166C at1r , the severity of COVID-19 and oxygen dependency is higher as compared to the A allele carriers, possibly, due to cardiovascular disorders.

The aim: Of our study was to establish how the biological rhythm of human affects the reparative functions of the body in terms of odontogenic purulent-inflammatory diseases of the maxillofacial localization. Materials and methods: The research was conducted on the basis of the Department of Maxillofacial Surgery on the basis of «Poltava Regional Clinical Hospital. M.V. Sklifosovsky». A total of 40 patients with odontogenic phlegmons of maxillofacial localization. Results: On the first day of the study, the indicators of the clinical condition of patients did not have a significant difference in all study groups. On the 3rd day of all studied groups, the number of points probably decreased compared to the first day of the study by 22.5%, 23.1%, 23.7%, 22.7%, respectively. On day 5, we have observed a significant difference between the previous results in all groups: 1a - 26.6%, 1b - 23.8%, 2a - 23.9%, 2b - 24.0%. Conclusions: The most effective treatment results were observed in patients of the morning chronotype who underwent surgery in the morning. Thus, the influence of the morning chronotype of the circadian rhythm on the course of reparative processes is manifested in the later stages of reparative regeneration.