In Kazakhstan, there is insufficient data on genetic epilepsy, which has its own clinical and management implications. Thus, this study aimed to use whole genome sequencing to identify and evaluate genetic variants and genetic structure of early onset epilepsy in the Kazakhstani pediatric population. In this study, for the first time in Kazakhstan, whole genome sequencing was carried out among epilepsy diagnosed children. The study involved 20 pediatric patients with early onset epilepsy and no established cause of the disease during the July–December, 2021. The average age at enrolment was 34.5 months, with a mean age at seizure onset of 6 months. Six patients (30%) were male, and 7 were familial cases. We identified pathogenic and likely pathogenic variants in 14 (70%) cases, among them, 6 novel disease gene variants (KCNQ2, CASK, WWOX, MT-CO3, GRIN2D, and SLC12A5). Other genes associated with the disease were SCN1A (x2), SLC2A1, ARX, CACNA1B, PCDH19, KCNT1, and CHRNA2. Identification of the genetic causes in 70% of cases confirms the general structure of the etiology of early onset epilepsy and the necessity of using NGS in diagnostics. Moreover, the study describes new genotype-phenotypic correlations in genetic epilepsy. Despite certain limitations of the study, it can be concluded that the genetic etiology of pediatric epilepsy in Kazakhstan is very broad and requires further research.

Aeromonas spp. are opportunistic pathogens that are widely distributed in water sources, with several species being associated with fish and human diseases. We have previously identified an Aeromonas AB005 isolate from diseased Acipencer baerii. This isolate was identified as A. hydrophila based on the 16S rRNA and gyrB gene sequences. However, this novel strain does not produce indole and tested negative for ornithine decarboxylase and d-xylose fermentation—differences that set it apart from typical A. hydrophila strains. In the present study, this strain was subjected to whole-genome sequencing and compared with the genomes of the type strain (Aeromonas hydrophila ATCC 7966^T) and other Aeromonas spp. Comprehensive genome analysis suggests that AB005 represents a distinct species within the genus. The draft genome of the AB005 strain comprises 4,780,815 base pairs with a GC content of 61.2% and contains 6104 predicted protein-coding sequences along with numerous genes implicated in antibiotic resistance. The core/pan-genome analysis reveals extensive genetic diversity, indicative of a dynamic genomic structure. These findings collectively underscore the taxonomic distinction of the AB005 strain as a novel species and highlight its potential pathogenic implications in aquaculture and public health settings.

Cardiometabolic disorders, including obesity, insulin resistance and type 2 diabetes mellitus, remain major biomedical problems closely linked to vascular complications. Dipeptidyl peptidase-4 (DPP-4) is a clinically validated therapeutic target because inhibition of this enzyme prolongs the activity of incretin hormones and supports glucose-dependent insulin secretion. This review compiles and critically evaluates plant-derived DPP-4 inhibitors, with emphasis on chemical class, enzyme source, quantitative activity, assay interpretability, and the translational relevance of reported findings. The available literature indicates that flavonoids and polyphenolic compounds dominate the field, although assay heterogeneity, medium effects, potential aggregation, and insufficient selectivity data limit interpretation. Among natural scaffolds, chalcones and aurones, including lanceoletin, leptosidin, xanthoangelol, chalconaringenin 2′-O-β-D-glucopyranoside, and aureusidin 6-O-β-D-glucopyranoside, represent comparatively well-supported lead-like scaffolds that warrant further standardized evaluation. The evidence does not support using plant-derived DPP-4 inhibitors as substitutes for approved antidiabetic drugs. Their greatest value lies in expanding chemical space and providing lead-like scaffolds for standardized potency, selectivity, kinetic and preclinical validation.

Introduction. Colorectal cancer (CRC) ranks as the second leading cause of cancer mortality and the third most common cancer worldwide. Recent statistics reveal a troubling rise in CRC incidence among adults under 50 in high-income countries, with rates increasing 1-4% annually. While screening advancements, including colonoscopy, have improved early detection and survival rates, metastatic cases with KRASmutations remain challenging due to limited treatment options and mutation-driven resistance mechanisms. Aim. The present study aims to analyze the clinical significance of multi-platform verification of KRAS gene mutation in a particular clinical case in order to optimize personalized treatment strategies for patients with KRAS-positive metastatic colorectal cancer. Materials and methods. Our study reports the case of a 58-year-old female diagnosed with advanced-stage rectal adenocarcinoma with KRASmutation and multi-organ metastasis. Following partial intestinal obstruction, the patient underwent resection surgery with cholecystectomy and metastasectomy, followed by FOLFOX chemotherapy and targeted therapy (TT). Despite initial stabilization, metastasis progressed to the lungs and liver. Multiplatform genetic analysis, including Next generation sequencing (NovaSeq 6000), Sanger sequencing, and droplet digital PCR (ddPCR), was employed to confirm KRAS variant status, highlighting minor platform-based discrepancies with clinical relevance. Discussion. KRAS mutations profoundly affect CRC treatment strategies, particularly in relation to EGFR inhibitor eligibility. Multi-platform validation ensures accurate variant detection, critical for clinical decision-making. This case emphasizes the necessity of complementary assays, given the observed KRAS mutation’s influence on therapeutic outcomes. Cross-platform diagnostic guidelines are advocated to standardize detection thresholds and improve precision in treatment planning. Conclusion. This case underscores the clinical significance of multiplatform KRAS mutation validation in metastatic CRC, highlighting the potential for improved diagnostic protocols to optimize personalized treatment strategies for KRAS-mutant CRC patients. Актуальность. Колоректальный рак (КРР) является второй по значимости причиной смертности от рака и третьей по распространенности в мире. Последние статистические данные свидетельствуют о тревожном росте заболеваемости КРР среди взрослых в возрасте до 50 лет в странах с высоким уровнем дохода, причем показатели увеличиваются на 1-4% в год. В то время как достижения в области скрининга, включая колоноскопию, позволили улучшить раннее выявление и выживаемость, случаи метастазирования с мутациями KRAS остаются сложными из-за ограниченных возможностей лечения и механизмов резистентности, обусловленных мутациями. Цель. Настоящее исследование направлено на анализ клинической значимости много платформенной проверки мутации гена KRAS при частном клиническом случае с целью оптимизации персонализированных стратегий лечения пациентов с KRAS -позитивным метастатическим колоректальным раком. Материалы и методы. В данном исследовании сообщается о случае 58-летней женщины с диагнозом аденокарцинома прямой кишки на поздней стадии с мутацией KRAS и полиорганными метастазами. После частичной кишечной непроходимости пациентке была проведена резекция с холецистэктомией и удалением метастазов, а затем химиотерапия по методу FOLFOX и таргетная терапия (ТТ). Несмотря на первоначальную стабилизацию, метастазы прогрессировали в легких и печени. Для подтверждения статуса варианта KRAS был использован мультиплатформенный генетический анализ, включающий секвенирование следующего поколения (NovaSeq 6000), секвенирование по Сэнгеру и капельную цифровую ПЦР (ddPCR), что выявило незначительные несоответствия между платформами и клинической значимостью. Обсуждение. Мутации KRAS существенно влияют на стратегии лечения КРР, особенно в отношении приемлемости ингибиторов EGFR. Мультиплатформенная валидация обеспечивает точное выявление вариантов, что имеет решающее значение для принятия клинических решений. Данный случай подчеркивает необходимость дополнительных анализов, учитывая влияние мутации KRAS на результаты лечения. Рекомендуется использовать разные...

Background: The high prevalence of heart failure with preserved ejection fraction (HFpEF) in patients with metabolic dysfunction emphasizes the urgent need for novel therapeutic strategies [1]. Dual agonists of the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors have demonstrated promising cardiometabolic effects in both preclinical and clinical settings [2]. This thesis is focused on the development of a structured clinical trial protocol to evaluate the efficacy and safety of dual GIP/GLP-1 receptor agonist therapy in patients with HFpEF in Kazakhstan. Objective: To develop a scientifically valid and ethically approved protocol to assess the effects of dual GIP/GLP-1 receptor agonists on cardiac function, metabolic control, and quality of life in HFpEF patients. Materials and Methods: This is a non-randomized, prospective, controlled clinical trial involving 120 patients with HFpEF (EF ≥45%) and type 2 diabetes. Participants will be assigned to two groups: 60 patients will receive four dose levels of a dual GIP/GLP-1 receptor agonist, and 60 will receive standard therapy. The intervention includes weekly subcutaneous injections for 40 weeks, with dose escalation every four weeks. The primary endpoint is change in NT-proBNP levels. Secondary endpoints include changes in body weight, glycemic control, and quality of life. Ethical approval was obtained from the Local Bioethics Committee of “National Laboratory Astana”. All study documentation and insurance are completed, along with official authorization from the Ministry of Health of the Republic of Kazakhstan for the importation of the investigational medicinal product (a dual GIP/GLP-1 receptor agonist). Results: It is hypothesized that dual GIP/GLP-1 receptor agonist therapy will lead to significant improvements in cardiac biomarkers, functional status, and metabolic parameters compared to placebo, with a favorable safety profile. Conclusion: This protocol establishes a comprehensive clinical framework to assess the dual metabolic and cardiac effects of GIP/GLP-1 receptor agonists in patients with HFpEF and could inform future therapeutic strategies for this challenging patient group. Acknowledgement: The study was supported by grants from the Ministry of Science and Higher Education of the Republic of Kazakhstan (AP23490249), (AR19677442), (BR24993023), (BR24992841), (BR21881970), and Nazarbayev University CRP (211123CRP1608) Key words: heart failure, GIP/GLP-1 receptor agonist, clinical protocol.

We thank the authors of the Comment