Structure and Functions of Human Serum Albumin in Normal Conditions and in Patients with Liver Cirrhosis

The aim: to highlight the main points of albumin synthesis, posttranslational modifications and functions in normal conditions and in patients with liver cirrhosis.Key points. Albumin is the most abundant protein in blood plasma. Along with oncotic properties, albumin performs transport, antioxidant, immunomodulatory and endothelioprotective functions. Serum albumin in patient with liver cirrhosis undergoes modifications, leading to functional impairment. Human serum albumin is a compaund of human mercaptalbumin with cysteine residues having a reducing ability, and oxidized human non-mercaptalbumin. The proportion of irreversibly oxidized non-mercaptalbumin-2 with impaired functional activity increases in liver cirrhosis.Conclusion. The conformational structure of the albumin molecule plays an important role in maintaining its non-oncotic functions. Non-oncotic functions depend on albumin conformation. Further investigation of albumin conformation and albumin functions in patients with hepatic insufficiency can serve as an additional criterion for assessing the severity of cirrhosis and predictor of complications may become an additional criterion to new clinical applications and treatment strategies of liver failure

The Role of Correcting Structural and Functional Albumin Properties in Ascites Control in Decompensated Cirrhotic Patients

Аim: to study the structural and functional characteristics of albumin in patients with decompensated cirrhosis, their relationship with ascites; to identify the relationship between improvement in albumin characteristics and regression of ascites.Materials and methods. Fifty patients with decompensated liver cirrhosis and ascites were divided into groups. The first group received standard treatment for cirrhosis, the second — standard treatment and replacement therapy with 20 % human albumin solution at a dose of 200 mL per week for 3 months.Results. The value of the native conformation of albumin and the functional parameters of albumin were significantly lower than in the group of healthy individuals (p < 0.001). With the severity of ascites, the native conformation index (DR), which characterizes the structural usefulness of the albumin molecule, decreased. Median DR for ascites stage I (IAC) was –1.69, II grade — –2.28, III grade — –2.42 (p < 0.05). Replacement therapy with albumin allowed to achieve regression of ascites in 48.4 % of patients, compared with 7.1 % in the standard treatment group. Along with clinical improvement, restoration of albumin structural and functional properties was observed in the albumin group. The mean serum albumin level at which ascites remained in remission for 3 months was 42.11 g/L (p < 0.001).Conclusions and discussion. The structural and functional characteristics of albumin were impaired in patients with decompensated cirrhosis and ascites. The severity of changes in the structural and functional properties of albumin depended on the severity of ascites. The regression of ascites was accompanied by the restoration of the functional and structural usefulness of albumin against the backdrop of albumin replacement therapy. The criterion for stopping transfusion therapy with albumin can be the achievement of a serum albumin level of 42.11 ± 7.04 g/L, DR — 1.05, BE — 73.51 %, RTQ — 75.10 %, DTE — 72.71 %

Changes in the Structural and Functional Albumin Properties in Patients with Decompensated Liver Cirrhosis

Аim: to conduct a comparative analysis of serum albumin's structural and functional properties in decompensated cirrhotic patients by means of spin prob EPR spectroscopy.Materials and methods. The main study group included 70 patients with decompensated liver cirrhosis and ascites. The control group consisted of 12 healthy volunteers, comparable in gender and age, without liver diseases. To assess the structural and functional ability, serum albumin was analyzed by EPR spectroscopy.Results. Albumin levels within reference intervals were found in 37 patients (59.8 %). The native albumin index decrease in cirrhotic patients as the disease progressed with the lowest values in the Child – Pugh C group (p < 0.001). The binding efficiency of albumin decreased in accordance with the severity of cirrhosis with minimal albumin binding capacity in the Child – Pugh C (Me = 25.43 %; n = 30; p < 0.001). The transport activity of RTQ albumin decreased in patients with decompensated cirrhosis, the lowest transport ability was observed in the Child – Pugh C group (Me = 26.09 %). In patients with decompensated disease the detoxification potential was significantly reduced: Child – Pugh B — Me = 44.03 %; Child – Pugh C — Me =17.16 %. Despite the normal values of serum albumin in 72.5% of patients with cirrhosis B and in 26.7% in the cirrhosis C group, only 12.3% in the cirrhosis B group had normal albumin function and in cirrhosis C nо patients had normal albumin function.Conclusion. There were not only serum concentration depletion in cirrhotic patients, but also albumin physiological non-oncotic properties were violated. The severity of these changes increased with the progression of cirrhosis. Our data allow us to raise the question of the need to use the EPR test to determine indications for albumin replacement therapy in patients with cirrhosis and the presence of ascites, even at normal values of its serum concentration

Features of proinflammatory cytokine production in patients with allergic rhinitis combined with <i>Helicobacter pylori</i>-associated pathologies

Investigating a role for pro- and anti-inflammatory cytokines in immune and inflammatory response represents one of the most pressing topics in current immunology. There have been accumulated a great body of data regarding the cytokine status during inflammatory processes in gastrointestinal tract. However, many issues remain poorly elucidated. Moreover, most of the studies were mainly aimed at examining biopsy material cytokines collected from various parts of the gastrointestinal tract or gastric juice. Here we present the data on investigating the features of cytokine production in patients with allergic rhinitis combined with H. pylori-associated diseases of the upper gastrointestinal tract. A total of 225 patients aged 18 to 40 years (mean age 29.5±6.74 years) were examined, among which 43 patients suffered from allergic rhinitis, 66 patients had inflammatory diseases of the upper gastrointestinal tract (chronic gastritis/gastroduodenitis), and 69 patients — allergic rhinitis with concomitant inflammatory diseases of the upper gastrointestinal tract. Patients were stratified to various study groups depending on diagnosed allergic rhinitis and H. pylori infection. Serum IL-6 and IL-8 level and complete blood cell count were measured. Statistical significance for difference in parameter frequencies between independent groups was assessed by using Fisher's exact test or χ2 criteria. It was shown that serum IL-6 level in H. pylori-negative patients was within the reference interval with single spikes, whereas its production was markedly increased in patients with H. pylori infection regardless of allergic pathology. Frequency of subjects with elevated serum IL-8 level was comparable between groups of patients with gastrointestinal diseases, but significantly higher than that one in the control group. An interdependence between serum IL-8 level and white blood cell count was found, which is of interest for predicting development of the inflammatory process. Thus, the serum IL-8 level during the upper gastrointestinal tract inflammatory diseases was increased regardless of verified of H. pylori infection and allergic rhinitis, whereas increased IL-6 serum level was observed solely in H. pylori-positive patients

New treatment options for a patient with chronic heart failure and chronic obstructive pulmonary disease

Introduction. The number of  patients with chronic heart failure  (CHF) and chronic obstructive pulmonary disease  (COPD) is increasing every year. In both CHF and COPD, secondary mitochondrial dysfunction is observed. In this regard, the attention of researchers is attracted by drugs that have their therapeutic effects at the level of mitochondria, one of which is meldonium. Meldonium has proven itself in the treatment of various diseases, however, the evaluation of the clinical efficacy of meldonium has not yet been carried out in comorbid patients with CHF and COPD.Aim. To study the  effects of  meldonium as part of  basic therapy on the  clinical condition, the  main functional parameters of the heart and lungs, and the quality of life in patients with CHF and COPD.Materials and methods. The randomized open study included 60 patients with CHF II A stage, II–III FC (clinical recommendations of the RSC, OSSN 2020) and COPD I–III degree of airflow limitation (GOLD 2021 classification) in remission (age 45–70 years). The patients were divided into 2 groups: the 1st group – the main group (n = 30) with CHF and COPD took meldonium at a dosage of 1000 mg/day in addition to the basic therapy, the 2nd group – the control group (n = 30) was only on basic therapy for CHF and COPD. The observation period is 12 weeks.Results. In patients with CHF and COPD, in the dynamics of therapy with the inclusion of meldonium, as a result, the severity of clinical symptoms decreased, improvement was revealed in the main structural and functional parameters of the heart, external respiration function, and quality of life.Conclusions: a significant beneficial effect of combination therapy with the inclusion of meldonium on the clinical and functional parameters of the heart and lungs, indicators of quality of life in patients with CHF and COPD has been established, which makes it possible to recommend the use of meldonium as part of combination therapy in comorbid patients

Differential Phosphorylation of Ribosomal Proteins in Arabidopsis thaliana Plants during Day and Night

Protein synthesis in plants is characterized by increase in the translation rates for numerous proteins and central metabolic enzymes during the day phase of the photoperiod. The detailed molecular mechanisms of this diurnal regulation are unknown, while eukaryotic protein translation is mainly controlled at the level of ribosomal initiation complexes, which also involves multiple events of protein phosphorylation. We characterized the extent of protein phosphorylation in cytosolic ribosomes isolated from leaves of the model plant Arabidopsis thaliana harvested during day or night. Proteomic analyses of preparations corresponding to both phases of the photoperiod detected phosphorylation at eight serine residues in the C-termini of six ribosomal proteins: S2-3, S6-1, S6-2, P0-2, P1 and L29-1. This included previously unknown phosphorylation of the 40S ribosomal protein S6 at Ser-231. Relative quantification of the phosphorylated peptides using stable isotope labeling and mass spectrometry revealed a 2.2 times increase in the day/night phosphorylation ratio at this site. Phosphorylation of the S6-1 and S6-2 variants of the same protein at Ser-240 increased by the factors of 4.2 and 1.8, respectively. The 1.6 increase in phosphorylation during the day was also found at Ser-58 of the 60S ribosomal protein L29-1. It is suggested that differential phosphorylation of the ribosomal proteins S6-1, S6-2 and L29-1 may contribute to modulation of the diurnal protein synthesis in plants

High Light Induced Disassembly of Photosystem II Supercomplexes in Arabidopsis Requires STN7-Dependent Phosphorylation of CP29

Photosynthetic oxidation of water and production of oxygen by photosystem II (PSII) in thylakoid membranes of plant chloroplasts is highly affected by changes in light intensities. To minimize damage imposed by excessive sunlight and sustain the photosynthetic activity PSII, organized in supercomplexes with its light harvesting antenna, undergoes conformational changes, disassembly and repair via not clearly understood mechanisms. We characterized the phosphoproteome of the thylakoid membranes from Arabidopsis thaliana wild type, stn7, stn8 and stn7stn8 mutant plants exposed to high light. The high light treatment of the wild type and stn8 caused specific increase in phosphorylation of Lhcb4.1 and Lhcb4.2 isoforms of the PSII linker protein CP29 at five different threonine residues. Phosphorylation of CP29 at four of these residues was not found in stn7 and stn7stn8 plants lacking the STN7 protein kinase. Blue native gel electrophoresis followed by immunological and mass spectrometric analyses of the membrane protein complexes revealed that the high light treatment of the wild type caused redistribution of CP29 from PSII supercomplexes to PSII dimers and monomers. A similar high-light-induced disassembly of the PSII supercomplexes occurred in stn8, but not in stn7 and stn7stn8. Transfer of the high-light-treated wild type plants to normal light relocated CP29 back to PSII supercomplexes. We postulate that disassembly of PSII supercomplexes in plants exposed to high light involves STN7-kinase-dependent phosphorylation of the linker protein CP29. Disruption of this adaptive mechanism can explain dramatically retarded growth of the stn7 and stn7stn8 mutants under fluctuating normal/high light conditions, as previously reported

A Protein Phosphorylation Threshold for Functional Stacking of Plant Photosynthetic Membranes

Phosphorylation of photosystem II (PSII) proteins affects macroscopic structure of thylakoid photosynthetic membranes in chloroplasts of the model plant Arabidopsis. In this study, light-scattering spectroscopy revealed that stacking of thylakoids isolated from wild type Arabidopsis and the mutant lacking STN7 protein kinase was highly influenced by cation (Mg++) concentrations. The stacking of thylakoids from the stn8 and stn7stn8 mutants, deficient in STN8 kinase and consequently in light-dependent phosphorylation of PSII, was increased even in the absence of Mg++. Additional PSII protein phosphorylation in wild type plants exposed to high light enhanced Mg++-dependence of thylakoid stacking. Protein phosphorylation in the plant leaves was analyzed during day, night and prolonged darkness using three independent techniques: immunoblotting with anti-phosphothreonine antibodies; Diamond ProQ phosphoprotein staining; and quantitative mass spectrometry of peptides released from the thylakoid membranes by trypsin. All assays revealed dark/night-induced increase in phosphorylation of the 43 kDa chlorophyll-binding protein CP43, which compensated for decrease in phosphorylation of the other PSII proteins in wild type and stn7, but not in the stn8 and stn7stn8 mutants. Quantitative mass spectrometry determined that every PSII in wild type and stn7 contained on average 2.5±0.1 or 1.4±0.1 phosphoryl groups during day or night, correspondingly, while less than every second PSII had a phosphoryl group in stn8 and stn7stn8. It is postulated that functional cation-dependent stacking of plant thylakoid membranes requires at least one phosphoryl group per PSII, and increased phosphorylation of PSII in plants exposed to high light enhances stacking dynamics of the photosynthetic membranes