Publications by authors named "Kalinichenko A"

The Banff classification is useful for diagnosing renal transplant rejection. However, it has limitations due to subjectivity and varying concordance in physicians' assessments. Artificial intelligence (AI) can help standardize research, increase objectivity and accurately quantify morphological characteristics, improving reproducibility in clinical practice.

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Animal models of human neurological disorders provide valuable experimental tools which enable us to study various aspects of disorder pathogeneses, ranging from structural abnormalities and disrupted metabolism and signaling to motor and mental deficits, and allow us to test novel therapies in preclinical studies. To be valid, these animal models should recapitulate complex pathological features at the molecular, cellular, tissue, and behavioral levels as closely as possible to those observed in human subjects. Pathological states resembling known human neurological disorders can be induced in animal species by toxins, genetic factors, lesioning, or exposure to extreme conditions.

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Oxidative stress, a state of disrupted redox signaling, reactive oxygen species (ROS) overproduction, and oxidative cell damage, accompanies numerous brain pathologies, including aging-related dementia and Alzheimer's disease, the most common neurodegenerative disorder of the elderly population. However, a causative role of neuronal oxidative stress in the development of aging-related cognitive decline and neurodegeneration remains elusive because of the lack of approaches for modeling isolated oxidative injury in the brain. Here, we present a chemogenetic approach based on the yeast flavoprotein d-amino acid oxidase (DAAO) for the generation of intraneuronal hydrogen peroxide (HO).

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In the work-up of chronic enteropathies an underlying inborn error of immunity (IEI) should be considered in certain cases. IEI are rare, but approximately 10% of patients may present with symptoms of inflammatory bowel disease (IBD), which is a much more common entity. Patients with IEI associated IBD may show extraintestinal symptoms or signs, and are often refractory to conventional anti-inflammatory treatment.

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The immunological synapse is a complex structure that decodes stimulatory signals into adapted lymphocyte responses. It is a unique window to monitor lymphocyte activity because of development of systematic quantitative approaches. Here we demonstrate the applicability of high-content imaging to human T and natural killer (NK) cells and develop a pipeline for unbiased analysis of high-definition morphological profiles.

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Exocytosis of cytotoxic granules (CG) by lymphocytes is required for the elimination of infected and malignant cells. Impairments in this process underly a group of diseases with dramatic hyperferritinemic inflammation termed hemophagocytic lymphohistiocytosis (HLH). Although genetic and functional studies of HLH have identified proteins controlling distinct steps of CG exocytosis, the molecular mechanisms that spatiotemporally coordinate CG release remain partially elusive.

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Dysregulated immune responses are essential underlying causes of a plethora of pathologies including cancer, autoimmunity, and immunodeficiency. We here investigated 4 patients from unrelated families presenting with immunodeficiency, autoimmunity, and malignancy. We identified 4 distinct homozygous mutations in TNFRSF9 encoding the tumor necrosis factor receptor superfamily member CD137/4-1BB, leading to reduced, or loss of, protein expression.

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The use of point-of-care diagnostics can prevent a number of complications and leading to improved health outcomes for patients in critical condition. Research have shown that elongation of the preanalytic stage leading of errors of studies and changes the results of a number of laboratory parameters. The article presents the key problems associated with the elongation of the preanalytic stage and possible solutions to address the shortcomings of existing diagnostics.

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Article Synopsis
  • Researchers found biallelic mutations in the DEF6 gene in patients with an immune disorder and systemic autoimmunity, shedding light on how immune responses can malfunction.
  • The study revealed that these mutations disrupt the regulation of the CTLA-4 protein's movement to the surface of T cells, which is crucial for controlling immune responses.
  • The findings suggest that targeting DEF6 could be a potential strategy for treating autoimmune diseases and cancer, as one patient responded well to CTLA-4-Ig treatment.
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Rare, monogenetic diseases present unique models to dissect gene functions and biological pathways, concomitantly enhancing our understanding of the etiology of complex (and often more common) traits. Although inflammatory bowel disease (IBD) is a generally prototypic complex disease, it can also manifest in an early-onset, monogenic fashion, often following Mendelian modes of inheritance. Recent advances in genomic technologies have spurred the identification of genetic defects underlying rare, very early-onset IBD (VEO-IBD) as a disease subgroup driven by strong genetic influence, pinpointing key players in the delicate homeostasis of the immune system in the gut and illustrating the intimate relationships between bowel inflammation, systemic immune dysregulation, and primary immunodeficiency with increased susceptibility to infections.

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Background: The actin-interacting protein WD repeat-containing protein 1 (WDR1) promotes cofilin-dependent actin filament turnover. Biallelic WDR1 mutations have been identified recently in an immunodeficiency/autoinflammatory syndrome with aberrant morphology and function of myeloid cells.

Objective: Given the pleiotropic expression of WDR1, here we investigated to what extent it might control the lymphoid arm of the immune system in human subjects.

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Mucosal-associated invariant T (MAIT) cells are abundant innate-like T lymphocytes in mucosal tissues and recognize a variety of riboflavin-related metabolites produced by the microbial flora. Relevant issues are whether MAIT cells are heterogeneous in the colon, and whether the local environment influences microbial metabolism thereby shaping MAIT cell phenotypes and responses. We found discrete MAIT cell populations in human colon, characterized by the diverse expression of transcription factors, cytokines and surface markers, indicative of activated and precisely controlled lymphocyte populations.

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Aim: To evaluate the role of laparoscopic surgery for colorectal cancer in advanced age patients.

Material And Methods: 290 patients with colorectal cancer were enrolled including 121 patients with rectal cancer and 169 patients with colon cancer. Main group consisted of 171 patients over 60 years old, control group - 119 patients younger 60 years old.

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Aim: To assess advisability of video-assisted surgery in advanced age patients with colorectal cancer.

Material And Methods: The study involved 44 patients with large intestine tumors. There were 30 patients with colon cancer aged 78.

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Aim: To assess the role of endoscopic technologies in treatment of complicated forms of colorectal cancer.

Material And Methods: Our trial included patients after endoscopic intervention (n=18) and open surgery (n=11).

Results: Mean time of surgery in this group was 158.

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Aim: To evaluate endoscopic technologies in treatment of patients with colorectal cancer and severe comorbidities.

Material And Methods: Two groups of patients after endoscopic (group 1, n = 58) and open (group 2, n = 40) surgery were assessed.

Results: Comorbidities were observed in 90.

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Aim: To assess laparoscopic surgery in treatment of colon cancer patients.

Material And Methods: The results of laparoscopic treatment of patients with colorectal cancer are presented in the article. It was estimated the influence of various clinical parameters including age, gender, comorbidities, tumor localization and stage and complications on laparoscopic management of these patients.

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MHC class I-related molecule MR1 presents riboflavin- and folate-related metabolites to mucosal-associated invariant T cells, but it is unknown whether MR1 can present alternative antigens to other T cell lineages. In healthy individuals we identified MR1-restricted T cells (named MR1T cells) displaying diverse TCRs and reacting to MR1-expressing cells in the absence of microbial ligands. Analysis of MR1T cell clones revealed specificity for distinct cell-derived antigens and alternative transcriptional strategies for metabolic programming, cell cycle control and functional polarization following antigen stimulation.

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The planning of optimizing activities of out-patient service is appropriate to carry out examination of opinions of administrators of ambulatory medical organizations. The expertise of 70 head physicians and their deputies of treatment activities of ambulatory medical organizations of Novosibirsk determined directions of optimization of functioning of territorial polyclinic. The applied activities resulted in decreasing of indicators of period of visiting, and level of social deadaptation of patients.

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