Transcriptome profiling and analysis of patients with esophageal squamous cell carcinoma from Kazakhstan.

Esophageal squamous cell carcinoma (ESCC) is the predominant subtype of esophageal cancer in Central Asia, often diagnosed at advanced stages. Understanding population-specific patterns of ESCC is crucial for tailored treatments. This study aimed to unravel ESCC's genetic basis in Kazakhstani patients and identify potential biomarkers for early diagnosis and targeted therapies. ESCC patients from Kazakhstan were studied. We analyzed histological subtypes and conducted in-depth transcriptome sequencing. Differential gene expression analysis was performed, and significantly dysregulated pathways were identified using KEGG pathway analysis (p-value < 0.05). Protein-protein interaction networks were constructed to elucidate key modules and their functions. Among Kazakhstani patients, ESCC with moderate dysplasia was the most prevalent subtype. We identified 42 significantly upregulated and two significantly downregulated KEGG pathways, highlighting molecular mechanisms driving ESCC pathogenesis. Immune-related pathways, such as viral protein interaction with cytokines, rheumatoid arthritis, and oxidative phosphorylation, were elevated, suggesting immune system involvement. Conversely, downregulated pathways were associated with extracellular matrix degradation, crucial in cancer invasion and metastasis. Protein-protein interaction network analysis revealed four distinct modules with specific functions, implicating pathways in esophageal cancer development. High-throughput transcriptome sequencing elucidated critical molecular pathways underlying esophageal carcinogenesis in Kazakhstani patients. Insights into dysregulated pathways offer potential for early diagnosis and precision treatment strategies for ESCC. Understanding population-specific patterns is essential for personalized approaches to ESCC management.

Comorbid Conditions in Persons Exposed to Ionizing Radiation and Veterans of the Soviet-Afghan War: A Cohort Study in Kazakhstan.

OBJECTIVES: This study investigated the prevalence and characteristics of comorbid conditions in patients exposed to ionizing radiation and those who were involved in the Soviet-Afghan war. METHODS: This study analyzed the frequency and spectrum of morbidity and comorbidity in patients over a long-term period (30-35 years) following exposure to ionizing radiation at the Semipalatinsk nuclear test site or the Chornobyl nuclear power plant, and among participants of the Soviet-Afghan war. A cohort study, both prospective and retrospective, was conducted on 675 patients who underwent comprehensive examinations. RESULTS: Numerical data were analyzed using the Statistica 6 program. The results are presented as the mean±standard deviation, median, and interquartile range (25-75th percentiles). The statistical significance of between-group differences was assessed using the Student t-test and Pearson chi-square test. A p-value of less than 0.05 was considered statistically significant. We found a high prevalence of cardiovascular diseases, including hypertension (55.0%) and cardiac ischemia (32.9%); these rates exceeded the average for this age group in the general population. CONCLUSIONS: The cumulative impact of causal occupational, environmental, and ultra-high stress factors in the combat zone in participants of the Soviet-Afghan war, along with common conventional factors, contributed to the formation of a specific comorbidity structure. This necessitates a rational approach to identifying early predictors of cardiovascular events and central nervous system disorders, as well as pathognomonic clinical symptoms in this patient cohort. It also underscores the importance of selecting suitable methods and strategies for implementing treatment and prevention measures.

Role of Ubiquitination and Epigenetics in the Regulation of AhR Signaling in Carcinogenesis and Metastasis: "Albatross around the Neck" or "Blessing in Disguise".

The molecular mechanisms and signal transduction cascades evoked by the activation of aryl hydrocarbon receptor (AhR) are becoming increasingly understandable. AhR is a ligand-activated transcriptional factor that integrates environmental, dietary and metabolic cues for the pleiotropic regulation of a wide variety of mechanisms. AhR mediates transcriptional programming in a ligand-specific, context-specific and cell-type-specific manner. Pioneering cutting-edge research works have provided fascinating new insights into the mechanistic role of AhR-driven downstream signaling in a wide variety of cancers. AhR ligands derived from food, environmental contaminants and intestinal microbiota strategically activated AhR signaling and regulated multiple stages of cancer. Although AhR has classically been viewed and characterized as a ligand-regulated transcriptional factor, its role as a ubiquitin ligase is fascinating. Accordingly, recent evidence has paradigmatically shifted our understanding and urged researchers to drill down deep into these novel and clinically valuable facets of AhR biology. Our rapidly increasing realization related to AhR-mediated regulation of the ubiquitination and proteasomal degradation of different proteins has started to scratch the surface of intriguing mechanisms. Furthermore, AhR and epigenome dynamics have shown previously unprecedented complexity during multiple stages of cancer progression. AhR not only transcriptionally regulated epigenetic-associated molecules, but also worked with epigenetic-modifying enzymes during cancer progression. In this review, we have summarized the findings obtained not only from cell-culture studies, but also from animal models. Different clinical trials are currently being conducted using AhR inhibitors and PD-1 inhibitors (Pembrolizumab and nivolumab), which confirm the linchpin role of AhR-related mechanistic details in cancer progression. Therefore, further studies are required to develop a better comprehension of the many-sided and "diametrically opposed" roles of AhR in the regulation of carcinogenesis and metastatic spread of cancer cells to the secondary organs.

Unraveling the Complex Web of Mechanistic Regulation of Versatile NEDD4 Family by Non-Coding RNAs in Carcinogenesis and Metastasis: From Cell Culture Studies to Animal Models.

Discoveries related to an intriguing feature of ubiquitination have prompted a detailed analysis of the ubiquitination patterns in malignant cells. How the "ubiquitinome" is reshaped during multistage carcinogenesis has garnered significant attention. Seminal studies related to the structural and functional characterization of NEDD4 (Neuronal precursor cell-expressed developmentally downregulated-4) have consolidated our understanding at a new level of maturity. Additionally, regulatory roles of non-coding RNAs have further complicated the complex interplay between non-coding RNAs and the members of NEDD4 family. These mechanisms range from the miRNA-mediated targeting of NEDD4 family members to the regulation of transcriptional factors for a broader range of non-coding RNAs. Additionally, the NEDD4-mediated degradation of different proteins is modulated by lncRNAs and circRNAs. The miRNA-mediated targeting of NEDD4 family members is also regulated by circRNAs. Tremendous advancements have been made in the identification of different substrates of NEDD4 family and in the comprehensive analysis of the molecular mechanisms by which various members of NEDD4 family catalyze the ubiquitination of substrates. In this review, we have attempted to summarize the multifunctional roles of the NEDD4 family in cancer biology, and how different non-coding RNAs modulate these NEDD4 family members in the regulation of cancer. Future molecular studies should focus on the investigation of a broader drug design space and expand the scope of accessible targets for the inhibition/prevention of metastasis.

GASTRIC AND DUODENAL AMYLOIDOSIS IN AN HIV-INFECTED PATIENT: A CASE REPORT AND A LITERATURE REVIEW.

We report the case of a 38-year-old female with gastrointestinal amyloidosis who presented with acute abdominal pain. The computed tomography scan showed that the patient had generalized lymphadenopathy. This clinical picture with absolute leukocytosis was interpreted as an acute secondary bacterial process of unspecified etiology with generalized lymphadenopathy. The patient was administered a broad-spectrum antibacterial drug and detoxication therapy. The upper endoscopy revealed bleeding of unknown origin. After a 2-day conservative hemostatic therapy, gastric tumor involvement was suggested during control endoscopy. The human immunodeficiency virus (HIV) antibodies were found with the following confirmation of their specificity by immunoblotting. Histopathological study of the biopsy specimens made it possible to diagnose gastrointestinal AA/AL-amyloidosis complicated by gastrointestinal bleeding.

Bufalin-Mediated Regulation of Cell Signaling Pathways in Different Cancers: Spotlight on JAK/STAT, Wnt/ß-Catenin, mTOR, TRAIL/TRAIL-R, and Non-Coding RNAs.

The renaissance of research into natural products has unequivocally and paradigmatically shifted our knowledge about the significant role of natural products in cancer chemoprevention. Bufalin is a pharmacologically active molecule isolated from the skin of the toad Bufo gargarizans or Bufo melanostictus. Bufalin has characteristically unique properties to regulate multiple molecular targets and can be used to harness multi-targeted therapeutic regimes against different cancers. There is burgeoning evidence related to functional roles of signaling cascades in carcinogenesis and metastasis. Bufalin has been reported to regulate pleiotropically a myriad of signal transduction cascades in various cancers. Importantly, bufalin mechanistically regulated JAK/STAT, Wnt/ß-Catenin, mTOR, TRAIL/TRAIL-R, EGFR, and c-MET pathways. Furthermore, bufalin-mediated modulation of non-coding RNAs in different cancers has also started to gain tremendous momentum. Similarly, bufalin-mediated targeting of tumor microenvironments and tumor macrophages is an area of exciting research and we have only started to scratch the surface of the complicated nature of molecular oncology. Cell culture studies and animal models provide proof-of-concept for the impetus role of bufalin in the inhibition of carcinogenesis and metastasis. Bufalin-related clinical studies are insufficient and interdisciplinary researchers require detailed analysis of the existing knowledge gaps.

Suppressive effects of bioactive herbal polysaccharides against different cancers: From mechanisms to translational advancements.

BACKGROUND: Fueled by rapidly evolving comprehension of multifaceted nature of cancers, recently emerging preclinical and clinical data have supported researchers in the resolution of knowledge gaps to deepen the understanding of the molecular mechanisms. The extra-ordinary and bewildering chemical diversity encompassed by biologically active natural products continues to be of relevance to drug discovery. Accumulating evidence has spurred a remarkable evolution of concepts related to pharmacological target of oncogenic signaling pathways by polysaccharides in different cancers. PURPOSE: The objective of the current review is to provide new insights into study progress on anticancer effects of bioactive herbal polysaccharides. METHODS: PubMed, Scopus, Web of Science, Embase, and other databases were searched for articles related to anticancer effects of polysaccharides. Searches were conducted to locate relevant publications published up to October 2022. RESULTS: Polysaccharides have been reported to pleiotropically modulate TGF/SMAD, BMP/SMAD, TLR4, mTOR, CXCR4 and VEGF/VEGFR cascades. We have also summarized how different polysaccharides regulated apoptosis and non-coding RNAs. Additionally, this mini-review describes increasingly sophisticated understanding related to polysaccharides mediated tumor suppressive and anti-metastatic effects in tumor-bearing mice. We have also provided an overview of the clinical trials related to chemopreventive role of polysaccharides. CONCLUSION: Genomic and proteomic findings from these studies will facilitate 'next-generation' clinical initiatives in the prevention/inhibition of cancer.

Regulation of Cell Signaling Pathways and Non-Coding RNAs by Baicalein in Different Cancers.

Landmark discoveries in molecular oncology have provided a wide-angle overview of the heterogenous and therapeutically challenging nature of cancer. The power of modern 'omics' technologies has enabled researchers to deeply and comprehensively characterize molecular mechanisms underlying cellular functions. Interestingly, high-throughput technologies have opened new horizons for the design and scientific fool-proof evaluation of the pharmacological properties of targeted chemical compounds to tactfully control the activities of the oncogenic protein networks. Groundbreaking discoveries have galvanized the expansion of the repertoire of available pharmacopoeia to therapeutically target a myriad of deregulated oncogenic pathways. Natural product research has undergone substantial broadening, and many of the drugs which constitute the backbone of modern pharmaceuticals have been derived from the natural cornucopia. Baicalein has gradually gained attention because of its unique ability to target different oncogenic signal transduction cascades in various cancers. We have partitioned this review into different sub-sections to provide a broader snapshot of the oncogenic pathways regulated by baicalein. In this review, we summarize baicalein-mediated targeting of WNT/ß-catenin, AKT/mTOR, JAK/STAT, MAPK, and NOTCH pathways. We also critically analyze how baicalein regulates non-coding RNAs (microRNAs and long non-coding RNAs) in different cancers. Finally, we conceptually interpret baicalein-mediated inhibition of primary and secondary growths in xenografted mice.

Early integration of palliative care into oncological care: a focus on patient-important outcomes.

BACKGROUND: Globally, cancer remains one of the leading causes of mortality. Palliative care is designed to meet a range of cancer patients' priority issues, including the management of pain and other cancer-associated symptoms. Routine palliative care envisages the provision of not just medical therapy, but also psychological support, social support and spiritual assistance. What constitutes the best model for palliative care remains a matter of debate. AIM: This review was undertaken with the aim to discuss different aspects of early integration of palliative care into oncological care, with a focus on patient-important outcomes. METHODS: A comprehensive search of publications was conducted with a focus on integrative palliative care for incurable cancer patients. For this purpose, the following databases and search engines were used: Scopus, PubMed, Cochrane Library, Research Gate, Google Scholar, eLIBRARY and Cyberleninka. RESULTS: A comprehensive approach with early integration of different medical services appears to be the most promising. Integrative palliative care is best provided via specialised interdisciplinary teams, given that all members maintain systemic communications and regularly exchange information. This model ensures that timely and adequate interventions are provided to address the needs of patients. CONCLUSION: Further research is needed to pinpoint the most optimal strategies to deliver palliative care and make it as tailored to the patient's demands as possible.