The onset and progression of various disorders, including chronic urticaria, are associated with stress. The gut-brain-skin axis is used to describe correlations among the nervous system, gastrointestinal tract states and systemic and skin inflammation. We have summarized inflammatory and immune mechanisms underlying chronic urticaria and stress in the context of the gut-brain-skin axis. The study was aimed to show the relationships between substance P, the neurotransmitter, and diamine oxidase, the enzyme disrupting histamine in the gut of patients suffering from chronic urticaria. A total of 165 adults aged 18–68 were enrolled; 97 patients had chronic urticaria, the comparison group was formed of 68 nominally healthy individuals. ELISA (Cloud-Clone Corp; China) was used to simultaneously estimate serum levels of substance P, diamine oxidase, and histamine. We revealed a significant positive correlation (ρ = 0.5; p < 0.05) between substance P and diamine oxidase in patients with chronic urticaria and in the comparison group, which confirmed the existence of the gut-brain-skin axis. The paper provides theoretical background and new targets for treatment of chronic urticaria. The possibility of prevention and treatment of these disorders by modulation of gut microbiota is discussed, the place of diet and the lifestyle modification contributing to improvement of general health are determined.
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Today, the cell-based technologies are one of the instruments used for the cartilage tissue repair. Creation of a universal hypoimmunogenic cartilage tissue graft from the differentiated derivatives of induced pluripotent stem cells (iPSCs) might solve the problem of the lack of the cartilage cell product. However, currently there is little data on immunogenicity of such tissue-engineered preparations. The study was aimed to create a cartilage implant from the differentiated derivatives of the B2M-deficient iPSCs and assess its immunogenicity. The previously developed protocol was used to ensure differentiation of both wild-type and B2M knockout iPSCs into chondrocyte-like cells. After quality control of the resulting cell lines by conducting polymerase chain reaction and immunocytochemical assessment, the resulting cell lines were co-cultured with the peripheral blood mononuclear cells of a healthy donor. When co-cultivation was over, activation and degranulation of CD8+ T cells was assessed by flow cytometry analysis based on the CD69 and CD107a expression on the cell surface, respectively. The iPSC-derived chondrocytes expressed the cartilage tissue markers. Flow cytometry analysis revealed no substantial differences in immunogenicity between the derivatives of wild-type and B2M knockout iPSCs, as well as from the cartilage tissue cells of a healthy donor. Immunogenicity of chondrocyte-like cells was higher than that of hypoimmunogenic non-edited iPSCs. The B2M knockout iPSCs demonstrated a trend towards greater activation of CD8+ T cells. Thus, the B2M knockout in the iPSC-derived chondrocytes had no significant effect on the tissue immunogenicity. It is necessary to further edit the genes encoding MHC II and CD47 to obtain a less immunogenic product.
VIEWS 149
Community-acquired pneumonia (CAP) is a major cause of pediatric morbidity and mortality. Currently, there is no common approach to determination of CAP severity in children, which hampers early diagnosis and treatment of the disease. The study was aimed to determine clinical and laboratory predictors of severe CAP in children under 4 years of age. Analysis of clinical data, parameters of complete blood count (CBC), C-reactive protein (CRP) using nonparametric methods for hypothesis testing, univariate correlation analysis, cross-tabulation (Statistica 10.0), logistic regression, and ROC analysis (SPSS Statistics 20.0) was performed in 72 children aged 1 month to 3 years 11 months admitted to hospital due to CAP. Severe CAP was diagnosed in 16.7% of children. Causes of severe CAP included respiratory distress (moderate — 58.3%, severe — 16.7% of cases) and sepsis (25%). We identified significant clinical predictors of severe CAP: vomiting (OR 4.2), tachypnea (OR 28.3), chest wall retractions (OR 6), wheezing (OR 4), and the absence of rhinitis (OR 0.21). Isolated assessment of the CBC and CRP did not allow to predict CAP severity. We have developed a prediction model predicting severe CAP in children under 4 years of age based on the presence of rhinitis, tachypnea, as well as leukocyte count (sensitivity and specificity 91.7%). Thus, currently the main cause of severe CAP in children under 4 years of age is respiratory distress, in which wheezing predominates. Physical examination with an emphasis on detection of rhinitis and respiratory distress is essential for diagnosing severe CAP. The use of a pneumonia severity prediction model may contribute to improvement of management of CAP in patients under 4 years of age.
VIEWS 208
The growing proportion of antibiotic-resistant Klebsiella pneumoniae strains raises challenges to the healthcare system and requires the development of alternative treatment options. Bacteriophage therapy is one of such options. The study was aimed to isolate and describe bacteriophages effective against K. pneumoniae strains of clinically significant capsular types. The bacteriophages were isolated from the sewage and river water samples using the enrichment culture technique. The spectrum of lytic activity of the phages was tested on the collection of K. pneumoniae clinical isolates (n = 279). The studied bacteriophages lysed 52.8–100% of K. pneumoniae strains of respective capsular types: phage VKV295 lysed 100% of strains with the capsular type KL1, SAA231 — 52.8 of strains with KL2, NNK-G4 — 100% of strains with KL39, VSG32 — 66.7% of strains with KL41, NKA196 — 87.5% of strains with KL47, Rappa3 — 87.5% of strains with KL57, PEA128 — 95.5% of strains with KL64, and ChM-G5 — 69.6% of strains with KL102. Whole-genome sequencing and subsequent bioinformatic analysis revealed that the phages belong to the Autographiviridae family and are classified into three genera.The lytic spectrum of phages was limited to specific capsular types due to the presence of specific receptor-binding proteins, polysaccharide depolymerases. The isolated bacteriophages were strictly virulent, did not carry harmful genetic determinants, and had a specific host range, making them applicable in therapeutic practice for combating antibiotic-resistant infections caused by K. pneumoniae.
VIEWS 193
Currently, treatment of contaminated skin wounds aggravated by ischemia of superficial soft tissues is a problem that presents certain difficulties. The search for the new ways of treatment and drugs possessing a multidirectional effect is a relevant problem. In this study, we aimed to explore the peculiarities of wound evolution and the effectiveness of the designed combination of medicines and magnetic therapy in a contaminated skin wound case. For the experiment, we divided male Wistar rats into 3 groups and modeled a contaminated skin wound in each of the animals. In the first group, no treatment was performed, in the second, we used the developed combination (benzalkonium chloride, dexpanthenol, pentoxifylline and carboxymethylcellulose sodium salt, combined with magnetic therapy), in the third — ointment with dioxomethyltetrahydropyrimidine + chloramphenicol and magnetic therapy. Planimetry, acid-base balance registration, measurements of microhemocirculation and local temperature of the wound bed underpinned monitoring assessment of the wounds. At the end of the study, the wound area in the second group was 10.7 and 3.7 (p < ; 0.05 ) times smaller than in the first and third groups, respectively, and healing rate — 2.6 and 1.3 (p < 0.05 ) times faster. The maximum values of microhemocirculation and the lowest pH were registered in the second group. Thus, combination of drugs and magnetotherapy we designed promoted healing of a contaminated skin wound, which allows recommending this treatment method for further study at the preclinical level.
VIEWS 178
Despite the prospects of the approach to cell therapy of cartilage damage in humans involving autologous chondrocytes, similar technologies are just beginning to be introduced into medical practice in the Russian Federation. In this regard, the development of biomedical cell products (BCPs) for cartilage tissue repair is quite topical, while the use of organoid technology is the most close to the native tissue conditions. According to requirements of legislation of the Russian Federation, it is necessary to assess biodistribution characterizing migration potential of the cells, their tropism for body tissues following implantation within the framework of preclinical trials. The study was aimed to assess biodistribution of novel BCP based on human chondrocytes in the form of chondrospheres after subcutaneous implantation in Balb/c nude mice. Implantation to 12 mice was performed during the first phase, along with administration of saline to 12 control animals. Weighting and follow-up were conducted for 90 days. Then mice were withdrawn from the experiment to collect samples of organs and tissues for histological analysis of the implant, estimation of its viability, integration. During the second phase biodistribution was assessed by PCR in order to detect human DNA in the organ and tissue samples. Chondrospheres successfully integrated in the tissues surrounding the inoculation zones and formed cartilage tissue. No significant (p < 0.05) changes in weight were reported. No human DNA found in chondrosphere implantation zones was detected in the samples collected from other organs and tissues. BCP demonstrated no biodistribution across other tissues and organs of mice 90 days after implantation, which suggested that the product developed was safe.
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