Natural killer T (NKT) cells are unconventional T cells that are activated by glycolipid antigens. They can produce a variety of inflammatory and regulatory cytokines and, therefore, modulate multiple aspects of the immune response in different pathological settings, including autoimmunity. NKT cells have also been implicated in the immunopathogenesis of autoimmune hepatitis, and in this review we summarize and analyze the main studies investigating the involvement and/or homeostasis of NKT cells in this disease. In detail, the evidence from both basic and clinical research has been specifically analyzed. Even though the experimental murine models supported a relevant role of NKT cells in immune-mediated hepatic injury, very few studies specifically investigated NKT cell homeostasis in patients with autoimmune hepatitis; however, these initial studies reported some alterations of NKT cells in these patients, which may also correlate with the disease activity to some extent. Further clinical studies are needed to investigate the potential role and use of NKT cell analysis as a disease marker of clinical relevance, and to better understand the precise cellular and molecular mechanisms by which NKT cells contribute to the pathogenesis of autoimmune hepatitis.

Every year in the world, sepsis occurs in 31.5 million people, and the number of deaths reaches 5.3 million per year. There are not enough studies that describe etiological structure of sepsis pathogens in different groups of population of the Republic of Kazakhstan. In this study, we have investigated difference of local sepsis etiology and antibiotic susceptibility among children and adults. A total 200 blood samples were examined using the standard and express method of identification of bloodstream pathogens. The determination of antimicrobial sensitivity was carried out by the disc-diffusion method according to CLSI guidelines. Overall, 23/90 (25.5%) positive blood cultures were isolated from adult patients and 43/110 (39%) from pediatric patients. It was found that children are statistically more often affected with bacterial bloodstream infection than adults ( ). The Gram-positive bacteria are the leading cause of sepsis in both groups: S. epidermidis (35.5%) in pediatric patients and S. aureus (21.7%) in adults. However, statistical significance was detected in pediatric patients ( ). The number of resistant strains of S. epidermidis (MRSE) in the group of children was 66.7%, while in adults, all S. epidermidis was resistant to azithromycin and cefoxitin (MRSE). S. aureus strains from adult patients and children had a similar picture of antibiotic patterns. The proportion of MRSA in pediatric patients was 16, 6%, and in adult patients, 20%. Enterobacterales (39%) were the second cause of sepsis in adult patients. 62.5% of Enterobacterales strains isolated from adults were phenotypically identified as ESBL, while in pediatric patients, 25% of ESBL producers were isolated. We have noted the resistance to antibiotics that are prescribed according to protocols of treatment of the Republic of Kazakhstan in the strains isolated from the patient’s blood.

Our study was carried out to characterize respiratory tract microbiota in patients with “COVID-like pneumonia” in Kazakhstan and analyze differences between COVID-19 positive and negative groups. Sputum samples were collected from hospitalized patients, ≥18 years old, in the three cities in Kazakhstan with the highest COVID-19 burden in July 2020. Isolates were identified by MALDI-TOF MS. Susceptibility testing was performed by disk diffusion. We used SPSS 26 and MedCalc 19 for statistical analysis. Among 209 patients with pneumonia, the median age was 62 years and 55% were male. RT-PCR-confirmed SARS-CoV-2 cases were found in 40% of patients, and 46% had a bacterial co-infection. Co-infection was not associated with SARS-CoV-2 RT-PCR test results, but antibiotic use was. The most frequent bacteria were Klebsiella pneumoniae (23%), Escherichia coli (12%), and Acinetobacter baumannii (11%). Notably, 68% of Klebsiella pneumoniae had phenotypic evidence of extended-spectrum beta-lactamases in disk diffusion assays, 87% of Acinetobacter baumannii exhibited resistance to beta-lactams, and >50% of E. coli strains had evidence of ESBL production and 64% were resistant to fluoroquinolones. Patients with a bacterial co-infection had a higher proportion of severe disease than those without a co-infection. The results reinforce the importance of using appropriate targeted antibiotics and effective infection control practices to prevent the spread of resistant nosocomial infections.

18 young children (aged from 1 month old to 2 years old) with congenital heart disease were observed. During observation they were divided into 2 groups. Group I-8 children with CHD, not complicated by PAH. Group II 11 children with CHD, complicated by PAH. The content of serotonin and its transporter in platelets, the amount of serotonin in serum were determined. Serotonin content was determined by enzyme-linked immunosorbent assay. The study was performed using the Serotonin ELISA diagnostic kit, IBL Hamburg on the Evolis automated robotic station (BioRad). To determine the Sodium-Dependent serotonin transporter (SLC6A4) there was used the method of quantitative sandwich ELISA of Cusabio production. The main initiator of the development of PAH is development of endothelial dysfunction of the pulmonary vessels. Since the cause of this dysfunction is associated with functional disorders of the serotonergic system, our task was to determine the content of SERT and serotonin in platelets in the studied groups. We suggest that the serotonin transporter (SERT), which is responsible for the proliferation of the pulmonary artery smooth-muscle cells (PASMC), can be used as a biomarker for predicting and diagnosing PAH in children with CHD. The need for early biomarkers in the diagnosis of PAH in children is claimed by scientists from many countries of the world [1, 2]. The results of our studies showed a significant increase in the concentration of SERT in platelets in group II, compared with group I more than several times. The serotonin content in platelets in children of group II tended to decrease as compared with group I. Perhaps, an excessive increase in transporters in platelets is sufficient in itself for the induction of PASMC hyperplasia and the subsequent development of PAH. It is necessary to continue research in this direction, which will help to reveal and understand the molecular mechanisms by which SERT regulates the proliferation of PASMC and the role of serotonin and its transporter in the development of PAH in children.

Understanding immunoregulation in newborns can help to determine the pathophysiology of neonatal sepsis and will contribute to improve the diagnosis, prognosis, and treatment and remains an urgent and unmet medical need to understand hyperinflammation or hypoinflammation associated with sepsis in newborns. This study included infants (up to 4 days old). The “sepsis” criteria was a positive blood culture. C-reactive protein demonstrates a strong dependence on the pathogen etiology. Therefore, its diagnostic odds ratio in Gram-positive bacteremia was 2.7 and the sensitivity was 45%, while Gram-negative was 15.0 and 81.8%, respectively. A neutrophil-lymphocyte ratio above 1 and thrombocytopenia below 10⁹ cells/L generally do not depend on the type of pathogen and have a specificity of 95%; however, the sensitivity of these markers is low. nCD64 demonstrated good analytical performance and was equally discriminated in both Gram (+) and Gram (−) cultures. The sensitivity was 87.5–89%, and the specificity was 65%. The HLA-DR and programmed cell death protein study found that activation-deactivation processes in systemic infection is different at points of application depending on the type of pathogen: Gram-positive infections showed various ways of activation of monocytes (by reducing suppressive signals) and lymphocytes (an increase in activation signals), and Gram-negative pathogens were most commonly involved in suppressing monocytic activation. Thus, the difference in the bacteremia model can partially explain the problems with the high variability of immunologic markers in neonatal sepsis.

Colorectal cancer is one of the most often diagnosed malignant tumors. In Kazakhstan, high incidence of CC is registered along with other oncology diseases. Despite a significant progress in the disease treatment achieved lately, CC is still one of the major reasons of mortality due to oncologic...