Background: 14-3-3η is an intracellular protein also detected in the serum and synovial fluid of patients with rheumatoid arthritis (RA). It is closely related to disease activity and anti-cyclic citrullinated peptide antibody levels. However, the main source of 14-3-3η and the mechanism of its release into the extracellular space remain unclear. Addressing these two points was the main goal of the current study. Methods: The source of 14-3-3η was investigated by immunostaining RA synovial tissue. Fibroblast-like synoviocytes, CD4⁺ cells, and macrophages were selected as candidates among the various cell types in the synovial tissue. Phosphorylation of mixed-lineage kinase domain-like pseudokinase (MLKL) and cell death of macrophages were studied by phalloidin staining and electron microscopy after stimulation with an oxidative stress inducer (diamide) or tumour necrosis factor (TNF)-α. Extracellular 14-3-3η protein levels were examined by western blotting. Results: Macrophages from the synovial tissue from RA, but not osteoarthritis, showed dense and widespread cytoplasmic staining for the 14-3-3η protein, co-localized with peptidylarginine deiminase 4. Swelling and membrane rupture of macrophages were induced by treatment with TNF-α, but not interleukin (IL) 6/soluble IL-6 receptor (sIL-6R). Increased MLKL phosphorylation followed by necroptosis was also induced in TNF-α-stimulated macrophages. Necrostatin-1, a necroptosis inhibitor, antagonized MLKL phosphorylation. High levels of 14-3-3η were detected in the culture supernatants of macrophages stimulated with diamide and TNF-α, but not IL-6/sIL-6R. Conclusions: Macrophages that highly express 14-3-3η undergo TNF-α-induced necroptosis with damage to the cellular structure, resulting in the secretion of 14-3-3η into the extracellular space. The current study provides a novel mechanism for 14-3-3η level increase in the RA synovial fluid.

Background. Severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) infection during pregnancy was associated with a number of adverse pregnancy outcomes, including miscarriage, preeclampsia, preterm birth, and stillbirth. The virus persistence can last for a long time, and the consequences of a previous coronavirus infection are currently under study. Objectives. This study aimed to establish the clinical features of the course of pregnancy and childbirth in women with a history of asymptomatic coronavirus disease 2019 (COVID-19). Methods. This study was conducted in the Regional Perinatal Center N3 of Turkestan city, Kazakhstan. A total of 229 participants were enrolled comprising individuals with (n = 133, exposed group) from August to September 2021 with a history of COVID-19 and without one in the same period in 2019 (n = 96, unexposed group). Results. There is a statistically significant strong association between a history of COVID-19 and the development of oligohydramnios (φ = 0.743, p < 0.001), and medium strength between a history of COVID-19 and the presence of anemia (φ = 0.254, p < 0.001), abnormal development of the placenta (φ = 0.254, p < 0.011), cord entanglement (φ = 0.343, p = 0.000), low birth weight (φ = 0.356, p < 0.001) and stillbirth (φ = 0.293, p < 0.001). Conclusions. The past COVID-19 infection in pregnant women has long-term consequences in the form of placenta abnormal development and oligohydramnios; and, as a result, the development of adverse perinatal outcomes

Severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) infection during pregnancy was associated with a number of adverse pregnancy outcomes, including miscarriage, preeclampsia, preterm birth, and stillbirth. The virus persistence can last for a long time, and the consequences of a previous coronavirus infection are currently under study. This study aimed to establish the clinical features of the course of pregnancy and childbirth in women with a history of asymptomatic coronavirus disease 2019 (COVID-19). This study was conducted in the Regional Perinatal Center N3 of Turkestan city, Kazakhstan from August to September 2021. A total of 229 participants were enrolled comprising individuals with (n=133, exposed group) or without a history of COVID-19 (n=96, unexposed group). There is a statistically significant strong relationship between a history of COVID-19 and the development of oligohydramnios (φ=0.743, p<0.001); medium strength between a history of COVID-19 and the presence of anemia, abnormal development of the placenta, cord entanglement, low birth weight and stillbirth (p<0.001). The past COVID-19 infection in pregnant women have long-term consequences in the form of placenta abnormal development and oligohydramnios, and as a result, the development of adverse perinatal outcomes.

Background/Objectives: Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory lung disease characterized by irreversible airway obstruction. This study aims to investigate the associations between COPD and its phenotypes with polymorphic variants of the IREB2 and CHRNA5 genes in the Kazakhstan population. Methods: A case–control study was conducted involving 265 COPD patients and 267 controls. Genotyping of the IREB2 polymorphisms rs13180 and rs2568494, as well as CHRNA5 rs16969968 polymorphism, was performed using real-time polymerase chain reactions (Real-Time PCRs). Results: A higher frequency of the AA genotype of the IREB2 rs2568494 polymorphism was identified in COPD patients with moderate to very severe airflow obstruction (Chronic Obstructive Lung Disease (GOLD) stages II, III, and IV), with an odds ratio of 0.69 (95% CI = 0.23–2.10; Padj = 0.03). The IREB2 rs13180 polymorphism was significantly more frequent or prevalent in smokers and showed a correlation with FEV₁ (forced expiratory volume in one second) (β = 7.79, SE = 2.98, p = 0.01) and FEV₁/ FVC (forced vital capacity) (β = 9.51, SE = 2.95, p = 0.002). Additionally, the CC genotype of this polymorphism was associated with clinical manifestations of COVID-19 in COPD patients (χ²= 3,95, df = 2, p = 0.05). Conclusions: Our study identified a significant association between the IREB2 rs2568494 polymorphism and an increased risk of severe COPD. The IREB2 rs13180 polymorphism was linked to smoking behavior, as well as key lung function indicators, suggesting its potential role in disease progression and lung damage. Furthermore, the CC genotype of the IREB2 rs13180 polymorphism was associated with clinical manifestations of COVID-19 in COPD patients, indicating a potential impact of this genetic variant on susceptibility to viral infections in this population.

Annotation Background Liver damage during SARS-CoV-2 is more often manifested as part of a cytokine storm and is a predictor of a more severe course of the disease. However, there is scant information on spontaneous liver damage during coronavirus infection. Aims To report on the acute coronaviral hepatitis manifestations. Methods In our study, we analyzed two clinical cases with SARS-CoV-2 debuted with acute hepatitis. Results Patients who tested positive for coronavirus had symptoms of acute viral hepatitis, elevated transaminases titles and minimal lung involvement. Moreover, one of the patients developed diabetes for the first time. Steroid treatment resulted in improved liver function tests, clinical findings, but not diabetes. Conclusion These cases indicate that acute hepatitis can be an independent manifestation of SARS-CoV-2 and that liver damage can be combined with damage to the pancreas, causing diabetes. Timely therapy with an adequate dose of glucocorticosteroids helped to stop the progression of the disease and avoid complications. Key words: SARS-CoV-2, Acute Viral Hepatitis, Coronaviral Hepatitis.