Analysis of Gut Microbiota in Patients with Parkinson's Disease.

Gut microbiota of patients with Parkinson's disease and healthy volunteers was analyzed by the method of high throughput 16S rRNA sequencing of bacterial genomes. In patients with Parkinson's diseases, changes in the content of 9 genera and 15 species of microorganisms were revealed: reduced content of Dorea, Bacteroides, Prevotella, Faecalibacterium, Bacteroides massiliensis, Stoquefichus massiliensis, Bacteroides coprocola, Blautia glucerasea, Dorea longicatena, Bacteroides dorei, Bacteroides plebeus, Prevotella copri, Coprococcus eutactus, and Ruminococcus callidus, and increased content of Christensenella, Catabacter, Lactobacillus, Oscillospira, Bifidobacterium, Christensenella minuta, Catabacter hongkongensis, Lactobacillus mucosae, Ruminococcus bromii, and Papillibacter cinnamivorans. This microbiological pattern of gut microflora can trigger local inflammation followed by aggregation of α-synuclein and generation of Lewy bodies.

Neutron reflectivity measurement of protein A-antibody complex at the solid-liquid interface.

Chromatography is a ubiquitous unit operation in the purification of biopharmaceuticals yet few studies have addressed the biophysical characterisation of proteins at the solution-resin interface. Chromatography and other adsorption and desorption processes have been shown to induce protein aggregation which is undesirable in biopharmaceutical products. In order to advance understanding of how adsorption processes might impact protein stability, neutron reflectivity was used to characterise the structure of adsorbed immunoglobulin G (IgG) on model surfaces.

[INFLUENCE OF SAUSSUREA CONTROVERSA AND FILLIPENDULA ULMARIA EXTRACTS ON IMMUNOLOGICAL REACTIVITY OF RATS WITH EXPERIMENTAL OSTEOMYELITIS.].

The influence of Saussurea controversa DC and Fillipendula ulmaria (L.) Maxim extracts on the immunological reactivity of rats with experimental osteomyelitis has been studied. The application of these extracts on the background of antibiotic therapy normalized the immunological reactivity indices: (i) reduced the levels of total immunoglobulins, IgM and IgG and (ii) increased the percentage of active neutrophils and their absorption capacity, as well as the percentage of completion of phagocytosis.

Specific-ion effects on the aggregation mechanisms and protein-protein interactions for anti-streptavidin immunoglobulin gamma-1.

Non-native protein aggregation is common in the biopharmaceutical industry and potentially jeopardizes product shelf life, therapeutic efficacy, and patient safety. The present article focuses on the relationship(s) among protein-protein interactions, aggregate growth mechanisms, aggregate morphologies, and specific-ion effects for an anti-streptavidin (AS) immunoglobulin gamma 1 (IgG1). Aggregation mechanisms of AS-IgG1 were determined as a function of pH and NaCl concentration with sodium acetate buffer and compared to previous work with sodium citrate.

Protein adsorption, desorption, and aggregation mediated by solid-liquid interfaces.

Adsorption of proteins to solid-fluid interfaces is often empirically found to promote formation of soluble aggregates and larger, subvisible, and visible particles, but key stages in this process are often difficult to probe directly. Aggregation mediated by adsorption to water-silicon oxide (SiOx) interfaces, akin to hydrated glass surfaces, was characterized as a function of pH and ionic strength for alpha-chymotrypsinogen (aCgn) and for a monoclonal antibody (IgG1). A flow cell permitted neutron reflectivity for protein layers adsorbed to clean SiOx surfaces, as well as after successive "rinse" steps.

Investigating the structural impact of the glutamine repeat in huntingtin assembly.

Acquiring detailed structural information about the various aggregation states of the huntingtin-exon1 protein (Htt-exon1) is crucial not only for identifying the true nature of the neurotoxic species responsible for Huntington's disease (HD) but also for designing effective therapeutics. Using time-resolved small-angle neutron scattering (TR-SANS), we followed the conformational changes that occurred during fibrillization of the pathologic form of Htt-exon1 (NtQ42P10) and compared the results with those obtained for the wild-type (NtQ22P10). Our results show that the aggregation pathway of NtQ22P10 is very different from that of NtQ42P10, as the initial steps require a monomer to 7-mer transition stage.

Protein-protein interactions in dilute to concentrated solutions: α-chymotrypsinogen in acidic conditions.

Protein-protein interactions were investigated for α-chymotrypsinogen by static and dynamic light scattering (SLS and DLS, respectively), as well as small-angle neutron scattering (SANS), as a function of protein and salt concentration at acidic conditions. Net protein-protein interactions were probed via the Kirkwood-Buff integral G22 and the static structure factor S(q) from SLS and SANS data. G22 was obtained by regressing the Rayleigh ratio versus protein concentration with a local Taylor series approach, which does not require one to assume the underlying form or nature of intermolecular interactions.

Observation of small cluster formation in concentrated monoclonal antibody solutions and its implications to solution viscosity.

Monoclonal antibodies (mAbs) are a major class of biopharmaceuticals. It is hypothesized that some concentrated mAb solutions exhibit formation of a solution phase consisting of reversibly self-associated aggregates (or reversible clusters), which is speculated to be responsible for their distinct solution properties. Here, we report direct observation of reversible clusters in concentrated solutions of mAbs using neutron spin echo.

[Immunophenotypic characteristic of dendritic cells in bronchial asthma in conditions of extract opisthorchis felineus in vitro].

This work shows comparative characteristics of immunogenic properties of the extract of Opisthorchis felineus in different severity of asthma using antigen presenting dendritic cells in vitro. New data on the effect of Opisthorchis felineus on the expression of surface markers of dendritic cells (CD209, HLA-DR, CD83, CD86) were received. Pronounced expression of CD209, CD86 and HLA-DR on the surface of dendritic cells in mild and severe asthma compared with healthy individuals was shown.

Evaluation of hepatoprotective activity of water-soluble polysaccharide fraction of Stellaria media L.

Therapy of rats with CCl4 hepatitis with Stellaria media L. water-soluble polysaccharide fraction in a dose of 100 mg/kg reduces serum activities of transaminases (ALT and AST), alkaline phosphatase, bilirubin, and the thymol test values. In the liver, the density of inflammatory infiltration of the organ parenchyma, total count of necrotic hepatocytes, fatty and protein degeneration are reducing.

[Functional state of a sphingomyeline cycle and free radical lipid oxidation activity of a rat's liver during different phases of starvation].

The functional state of a sphingomyeline cycle and character of its mutual relations with the processes of free radical lipid oxidation during starvation of animals without any restriction of access to drinking water at 1, 2, 3 day (I phase) and 6 day (II phase of starvation) were studied at the liver of rats. The maximal values of the ceramide/sphingomyeline ratio and activity neutral sphingomyelinase and executive caspase-3 were reached in a liver of animals at the 3rd day of starvation. From the 3rd day of starvation the concentration of the tumour necrosis factor-alpha which is one of activators neutral sphingomyelinase was increase in rats blood serum.

Structural formation of huntingtin exon 1 aggregates probed by small-angle neutron scattering.

In several neurodegenerative disorders, including Huntington's disease, aspects concerning the earliest of protein structures that form along the aggregation pathway have increasingly gained attention because these particular species are likely to be neurotoxic. We used time-resolved small-angle neutron scattering to probe in solution these transient structures formed by peptides having the N-terminal sequence context of mutant huntingtin exon 1. We obtained snapshots of the formed aggregates as the kinetic reaction ensued to yield quantitative information on their size and mass.

[The interconnection between cytokines and the factors of bactericidal action of neutrophiles in patients operated on under the conditions of cardiopulmonary bypass].

The use of cardiopulmonary bypass (CPB) is associated with the development of a system inflammatory response. The subjects of the study were 48 patients with coronary heart disease (CHD), operated on under the condition of CPB. The following parameters were measured: the content of cation proteins and active oxygen forms in neutrophiles, the digesting capacity of these cells, and the serum levels of interleukins (IL)-1beta, 1ra, -4, -6, -8, and tumor necrosis factor-alpha (TNF-alpha).

[Functional status of peripheral blood monocyte in patients with Ixodes tick-borne borreliosis accompanied by opisthorchiasis].

The characteristics of the functional status of peripheral blood monocytes/macrophages in patients with Ixodes tick-borne acute borreliosis accompanied by opisthorchiasis invasion were studied. The study revealed a decrease in the phagocytic activity of monocytes and in the level of expression of cell receptors Fcgamma with the expression of cell receptors C3beta being normal.

[Peripheral blood mononuclear leucocytes in patients with drug-sensitive and drug-resistant pulmonary tuberculosis].

The authors studied functional characteristics of mononuclear leucocytes in patients with drug-sensitive and drug-resistant pulmonary tuberculosis. The study found decrease of the number of C3b- and Fcchi-receptorpositive monocytes and increase of their saturation activity in both categories of pulmonary tuberculosis before and after antituberculous therapy. The study revealed increase of interferons alpha and chi production and, at the same time, decrease of tumor necrosis factor alpha, which was more prominent in cases of drug-sensitive tuberculosis, and depression of interleukin 2 secretion, more prominent during chemotherapy in cases of drug-resistant tuberculosis.

[Hepatoprotectors containing phospholipids decrease the immunosuppressive effect of prednisolone in rats with experimental toxic hepatitis].

The experiments on rats with a model toxic hepatitis induced by tetrachloromethane showed that hepatoprotectors containing phospholipids (eplir and essentiale) introduced in combination with prednisolone decrease the immunodepressant effect of this glucocorticoid, as manifested by a decrease in the atrophy of thymus and an increase in the amount of blood lymphocytes, the number of splenic blasts, and the functional activity of mononuclear cells in C3b and Fc(gamma) receptors in peritoneal exudate.

[Clinical and immunologic correlations of gastroduodenal lesions in patients with bronchial asthma].

To study local immunity of the stomach in bronchial asthma (BA) and the role of some immunity factors deficiency in development of gastroduodenal disturbances in BA patients, we have examined 271 male and female patients aged 18 to 60 years with exogenic and mixed BA of different severity. Gastroduodenal erosions were endoscopically diagnosed in 61 (22.5%) patients.