Mechanisms Of Disease Development Research Articles

Construction of a fluorescence sensing platform based on RISC and CRISPR/Cas12a for the assay of Ago2 enzyme activity

PurposeArgonaute 2 (Ago2) is a protein with nucleic acid endonuclease activity and is ubiquitous in eukaryotic cells. Ago2 is a core member of RNA interference and is involved in important gene regulation in the body and the development of multiple tumors by affecting oncogenic or oncogenic gene expression. Ago2 is a potential tumor biomarker. Therefore, the assay of Ago2 activity can help monitor the disease progression and prognosis and contribute to the study of the mechanism of disease development. MethodsAgo2-based nucleic acid endonuclease activity cleaves the target hairpin nucleic acid chain and progressively stimulates the hybridization chain reaction (HCR) in the sensing strategy, causing signal amplification to form specific dsDNA, which then triggers the powerful non-selective single nucleic acid chain cleavage activity of the CRISPR/cas12a system and releases the fluorescence signal in the reporter probe. ResultsThe sensitive assay of Ago2 enzyme activity was achieved using the biofunctional properties of RNA-induced silencing complex (RISC) and CRISPR/Cas12a. Under the optimized conditions, the fluorescence signal intensity of the assay was positively correlated with the activity concentration of Ago2, with an excellent linear response range of 0.02–20 nM and a limit of detection (LOD) of 10 pM. When applied to the assay of Ago2 in cell lysates, the experimental recovery was 93.33%-107.08%, and the sensing platform was able to detect the Ago2 content in the presence of interference specifically. ConclusionTherefore, the fluorescence sensing platform successfully constructed in this paper is suitable for the assay of endogenous Ago2 activity in complex samples, and the assay method has the advantages of high specificity, sensitive detection, easy operation and low instrumentation requirements, which is expected to be applied to the actual sample assay in clinical settings. Meanwhile, it provides an assay direction for the biofunctional analysis of nucleases and a feasible direction for applying RISC and Crispr/Cas12a in sensing analysis.

Plasma exchange in neurology patients-experience from single center in Montenegro.

Plasma exchange (PE) is widely used in many immune-based neurological diseases. Our aim is to analyze characteristics of PE in neurological patients at the Clinical Center of Montenegro. Our study involved neurological patients treated with PE between January 2020 and April 2022. In total, 246 PEs were performed in 43 patients. We divided patients into 4 groups according to indications. In 8/9 multiple sclerosis (MS) patients a decrease of Expanded Dysability Status Scale at least 0.5 was verified. In 14/20 Guillain Barre syndrome patients reduction of Hughes was observed. Four patients with myasthenia gravis (MG) were treated with PE. The most heterogeneous group (4) consisted of patients in whom the mechanism of disease development is assumed to be immune system dysregulation. Fourteen patients had any adverse event. Our results show that PE is widely used and safe in the treatment of neurological diseases.

Management of alcoholic hepatitis: A clinical perspective.

Alcohol-associated liver disease is the primary cause of liver-related mortality worldwide and one of the most common indications for liver transplantation. Alcoholic hepatitis represents the most acute and severe manifestation of alcohol-associated liver disease and is characterized by a rapid onset of jaundice with progressive inflammatory liver injury, worsening of portal hypertension, and an increased risk for multiorgan failure in patients with excessive alcohol consumption. Severe alcoholic hepatitis is associated with a poor prognosis and high short-term mortality. During the COVID-19 pandemic, rates of alcohol-associated hepatitis have increased significantly, underscoring that it is a serious and growing health problem. However, adequate management of alcohol-associated hepatitis and its complications in everyday clinical practice remains a major challenge. Currently, pharmacotherapy is limited to corticosteroids, although these have only a moderate effect on reducing short-term mortality. In recent years, translational studies deciphering key mechanisms of disease development and progression have led to important advances in the understanding of the pathogenesis of alcoholic hepatitis. Emerging pathophysiology-based therapeutic approaches include anti-inflammatory agents, modifications of the gut-liver axis and intestinal dysbiosis, epigenetic modulation, antioxidants, and drugs targeting liver regeneration. Concurrently, evidence is increasing that early liver transplantation is a safe treatment option with important survival benefits in selected patients with severe alcoholic hepatitis not responding to medical treatment. This narrative review describes current pathophysiology and management concepts of alcoholic hepatitis, provides an update on emerging treatment options, and focuses on the need for holistic and patient-centred treatment approaches to improve prognosis.

Establishment and characterization of CSCRi006-A: an induced pluripotent stem cell line generated from a patient with Diamond-Blackfan Anemia (DBA) carrying ribosomal protein S19 (RPS19) mutation.

Diamond-Blackfan anemia (DBA) is a congenital hypoplastic anemia characterized by ineffective erythropoiesis. DBA is majorly caused by mutations in the ribosomal protein (RP) genes (Gadhiya and Wills in Diamond-Blackfan Anemia, https://www.statpearls.com/ ; 2023). A suitable disease model that yields a continuous supply of erythroid cells is required to study disease pathogenesis and drug discovery. Toward this, we reprogrammed dermal fibroblasts from a DBA patient with a heterozygous mutation c.22-23delAG in the RPS19 gene identified through exome sequencing. To generate induced pluripotent stem cells (iPSCs), we induced episomal expression of the reprogramming factors OTC3/4, L-MYC, LIN28, SOX2, and KLF4, and a p53 shRNA2. The DBA-iPSC line CSCRi006-A generated during this study was extensively characterized for its pluripotency and genome stability. The clone retained normal karyotype and showed high expression levels of pluripotency markers, OCT4, NANOG, SOX2, TRA-I-60, TRA-I-81, and SSEA4. It could differentiate into cells originating from all three germ cell layers, as identified by immunostaining for SOX17 (endoderm), Brachyury (mesoderm), and PAX6 (ectoderm). IPSCs provide a renewable source of cells for in vitro disease modeling. CSCRi006-A, a thoroughly characterized iPSC line carrying heterozygous RPS19 c.22-23delAG mutation, is a valuable cell line for the disease modeling of DBA. This iPSC line can be differentiated into different blood cell types to study the mechanisms of disease development and identify potential treatments.

GeNetOntology: identifying affected gene ontology terms via grouping, scoring, and modeling of gene expression data utilizing biological knowledge-based machine learning.

Introduction: Identifying significant sets of genes that are up/downregulated under specific conditions is vital to understand disease development mechanisms at the molecular level. Along this line, in order to analyze transcriptomic data, several computational feature selection (i.e., gene selection) methods have been proposed. On the other hand, uncovering the core functions of the selected genes provides a deep understanding of diseases. In order to address this problem, biological domain knowledge-based feature selection methods have been proposed. Unlike computational gene selection approaches, these domain knowledge-based methods take the underlying biology into account and integrate knowledge from external biological resources. Gene Ontology (GO) is one such biological resource that provides ontology terms for defining the molecular function, cellular component, and biological process of the gene product. Methods: In this study, we developed a tool named GeNetOntology which performs GO-based feature selection for gene expression data analysis. In the proposed approach, the process of Grouping, Scoring, and Modeling (G-S-M) is used to identify significant GO terms. GO information has been used as the grouping information, which has been embedded into a machine learning (ML) algorithm to select informative ontology terms. The genes annotated with the selected ontology terms have been used in the training part to carry out the classification task of the ML model. The output is an important set of ontologies for the two-class classification task applied to gene expression data for a given phenotype. Results: Our approach has been tested on 11 different gene expression datasets, and the results showed that GeNetOntology successfully identified important disease-related ontology terms to be used in the classification model. Discussion: GeNetOntology will assist geneticists and scientists to identify a range of disease-related genes and ontologies in transcriptomic data analysis, and it will also help doctors design diagnosis platforms and improve patient treatment plans.

Molecular testing raises thyroid nodule fine needle aspiration diagnostic value.

Thyroid fine needle aspiration biopsy (FNAB) remains indeterminate in 16%-24% of the cases. Molecular testing could improve the diagnostic accuracy of FNAB. This study examined the gene mutation profile of patients with thyroid nodules and analyzed the diagnostic ability of molecular testing for thyroid nodules using a self-developed 18-gene test. Between January 2019 and August 2021, 513 samples (414 FNABs and 99 formalin-fixed paraffin-embedded (FFPE) specimens) underwent molecular testing at Ruijin Hospital. Sensitivity (Sen), specificity (Spe), positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. There were 457 mutations in 428 samples. The rates of BRAF, RAS, TERT promoter, RET/PTC, and NTRK3 fusion mutations were 73.3% (n=335), 9.6% (n=44), 2.8% (n=13), 4.8% (n=22), and 0.4% (n=2), respectively. The diagnostic ability of cytology and molecular testing were evaluated in Bethesda II and V-VI samples. For cytology alone, Sen, Spe, PPV, NPV, and accuracy were 100%, 25.0%, 97.4%, 100%, and 97.4%; these numbers were 87.5%, 50.0%, 98.0%, 12.5%, and 86.2% when considering positive mutation, and 87.5%, 75.0%, 99.0%, 17.6%, and 87.1% when considering positive cytology or and positive mutation. In Bethesda III-IV nodules, when relying solely on the presence of pathogenic mutations for diagnosis, Sen, Spe, PPV, NPV, and AC were 76.2%, 66.7%, 94.1%, 26.8%, and 75.0%, respectively. It might be necessary to analyze the molecular mechanisms of disease development at the genetic level to predict patients with malignant nodules more accurately in different risk strata and develop rational treatment strategies and definite management plans.

The State of the Art in Transcriptomics and Proteomics of Clinically Relevant Sporothrix Species.

Proteomics provide a robust approach to profile and quantify proteins within cells, organs, or tissues, providing comprehensive insights about the dynamics of cellular processes, modifications, and interactions. Similarly, understanding the transcriptome is essential to decipher functional elements of the genome, unraveling the mechanisms of disease development and the molecular constituents of cells and tissues. Some thermodimorphic fungi of the genus Sporothrix cause sporotrichosis, a subcutaneous mycosis of worldwide relevance. The transcriptome and proteome of the main Sporothrix species of clinical interest can elucidate the mechanisms underlying pathogenesis and host interactions. Studies of these techniques can contribute to the advancement of novel diagnostic and therapeutic strategies. A literature review was carried out, addressing all articles based on proteomics using mass spectrometry and transcriptomics of Sporothrix spp. Twenty-one studies were eligible for this review. The main findings include proteins and genes involved in dimorphism, cell differentiation, thermotolerance, virulence, immune evasion, metabolism, cell adhesion, cell transport, and biosynthesis. With the spread and emergence of sporotrichosis in different countries, ongoing research efforts and new discoveries are welcome to advance knowledge about this mycosis and its agents.

Probiotics in Women and Pediatrics Health; A Narrative Review

Probiotic use to improve health is not new; but recently, it has attracted much attention concerning human health and diseases. The human gut is a delicate ecosystem where bacteria and host cells interact with each other. This is an important part of gut homeostasis and human development. Disruption of this sensitive ecosystem may have detrimental health repercussions linked to impaired gut microbiota (GM). GM were extensively examined as an underlying mechanism for disease development and progression. Additionally, it was used as a tailored method for preventing and treating disease. Because of the strong association between GM, health, and disease, there has been much interest in employing probiotics or living microorganisms, to regulate GM to prevent or cure specific diseases. Herein, probiotics' role in enhancing women's and pediatric well-being was addressed as a marker of disease and as therapeutic avenues; where we discussed probiotics indications, efficacy, safety profiles, and future prospects in clinical practice.

KATZNCP: a miRNA–disease association prediction model integrating KATZ algorithm and network consistency projection

BackgroundClinical studies have shown that miRNAs are closely related to human health. The study of potential associations between miRNAs and diseases will contribute to a profound understanding of the mechanism of disease development, as well as human disease prevention and treatment. MiRNA–disease associations predicted by computational methods are the best complement to biological experiments.ResultsIn this research, a federated computational model KATZNCP was proposed on the basis of the KATZ algorithm and network consistency projection to infer the potential miRNA–disease associations. In KATZNCP, a heterogeneous network was initially constructed by integrating the known miRNA–disease association, integrated miRNA similarities, and integrated disease similarities; then, the KATZ algorithm was implemented in the heterogeneous network to obtain the estimated miRNA–disease prediction scores. Finally, the precise scores were obtained by the network consistency projection method as the final prediction results. KATZNCP achieved the reliable predictive performance in leave-one-out cross-validation (LOOCV) with an AUC value of 0.9325, which was better than the state-of-the-art comparable algorithms. Furthermore, case studies of lung neoplasms and esophageal neoplasms demonstrated the excellent predictive performance of KATZNCP.ConclusionA new computational model KATZNCP was proposed for predicting potential miRNA–drug associations based on KATZ and network consistency projections, which can effectively predict the potential miRNA–disease interactions. Therefore, KATZNCP can be used to provide guidance for future experiments.

Pathological roles of macrophages in Leishmania infections.

Macrophages are the major host cells for Leishmania parasites, and determine the fate of infection by either limiting or allowing growth of the parasites, resulting in development or control of leishmaniasis, respectively. They also play important roles in causing pathological outcomes during Leishmania infection. The pathophysiology is complex and include a wide variety of molecular and cellular responses including enhancement of inflammatory responses by releasing cytokines, causing damages to surrounding cells by reactive oxygen species, or disordered phagocytosis of other cells. It is of note that disease severity in leishmaniasis sometimes does not correlate with parasite burdens, indicating that pathological roles of macrophages are not necessarily linked to their parasite-killing activities that are often defined by M1/M2 status. Here, we review the roles of macrophages in leishmaniasis with a focus on their pathological mechanisms in disease development.

Contribution of NOS3AS Variants to Susceptibility to Essential Hypertension: A Study in Kermanshah Province, Western Iran.

Hypertension (HTN) is a global health challenge and increase the risk of cardiovascular disease. Hypertension has a multifactorial course of evolution, with both genetic and environmental factors playing an important role. To date, a number of genes and pathways have been proposed to be associated with HTN, among which is Nitric Oxide pathway. NO levels can be regulated by reactive oxygen species (ROS), superoxide and post-transcriptional mechanisms, including sense-anti sense interactions. NOS3AS gene encodes an antisense RNA (sONE) which is complementary to NOS3 transcript in 662 nucleotides and may regulate NOS3 in a post-transcriptional manner. In this study, we sought to define the role of NOS3AS in the pathophysiology of essential HTN. A total of 131 cases with hypertension and 115 controls were enrolled in the study. Peripheral blood was drawn from all study participants after signing the informed consent form. Three variants (rs71539868, rs12666075 and rs7830) were investigated by Tetra-ARMS PCR method. The results were then statistically analyzed. We found statistically significant association between rs7830 TT genotype, rs12666075 GT and TT genotypes with susceptibility to HTN. We failed to observe association between rs71539868 and susceptibility to HTN. The present study showed a strong association between NOS3AS variants and susceptibility to hypertension in the population of Kermanshah province. Our results may shed more light on the mechanisms of disease development and may also help to better identify genetic predispositions and individuals at risk.

Induced Pluripotent Stem Cell-Based Modeling of Single-Ventricle Congenital Heart Diseases.

Congenital heart disease includes a wide variety of structural cardiac defects, the most severe of which are single ventricle defects (SVD). These patients suffer from significant morbidity and mortality; however, our understanding of the developmental etiology of these conditions is limited. Model organisms offer a window into normal and abnormal cardiogenesis yet often fail to recapitulate complex congenital heart defects seen in patients. The use of induced pluripotent stem cells (iPSCs) derived from patients with single-ventricle defects opens the door to studying SVD in patient-derived cardiomyocytes (iPSC-CMs) in a variety of different contexts, including organoids and chamber-specific cardiomyocytes. As the genetic and cellular causes of SVD are not well defined, patient-derived iPSC-CMs hold promise for uncovering mechanisms of disease development and serve as a platform for testing therapies. The purpose of this review is to highlight recent advances in iPSC-based models of SVD. Recent advances in patient-derived iPSC-CM differentiation, as well as the development of both chamber-specific and non-myocyte cardiac cell types, make it possible to model the complex genetic and molecular architecture involved in SVD development. Moreover, iPSC models have become increasingly complex with the generation of 3D organoids and engineered cardiac tissues which open the door to new mechanistic insight into SVD development. Finally, iPSC-CMs have been used in proof-of-concept studies that the molecular underpinnings of SVD may be targetable for future therapies. While each platform has its advantages and disadvantages, the use of patient-derived iPSC-CMs offers a window into patient-specific cardiogenesis and SVD development. Advancement in stem-cell based modeling of SVD promises to revolutionize our understanding of the developmental etiology of SVD and provides a tool for developing and testing new therapies.

Microprotein Dysregulation in the Serum of Patients with Atrial Fibrillation.

The incidence rate of atrial fibrillation (AF) has stayed at a high level in recent years. Despite the intensive efforts to study the pathologic changes of AF, the molecular mechanism of disease development remains unclarified. Microproteins are ribosomally translated gene products from small open reading frames (sORFs) and are found to play crucial biological functions, while remain rare attention and indistinct in AF study. In this work, we recruited 65 AF patients and 65 healthy subjects for microproteomic profiling. By differential analysis and cross-validation between independent datasets, a total of 4 microproteins were identified as significantly different, including 3 annotated ones and 1 novel one. Additionally, we established a diagnostic model with either microproteins or global proteins by machine learning methods and found the model with microproteins achieved comparable and excellent performance as that with global proteins. Our results confirmed the abnormal expression of microproteins in AF and may provide new perspectives on the mechanism study of AF.

Modified glucose as a sensor to track the metabolism of individual living endothelial cells - Observation of the 1602 cm−1 band called “Raman spectroscopic signature of life”

A relatively new approach to subcellular research is Raman microscopy with the application of sensors called Raman probes. This paper describes the use of the sensitive and specific Raman probe, 3-O-propargyl-d-glucose (3-OPG), to track metabolic changes in endothelial cells (ECs). ECs play a significant role in a healthy and dysfunctional state, the latter is correlated with a range of lifestyle diseases, particularly with cardiovascular disorders. The metabolism and glucose uptake may reflect the physiopathological conditions and cell activity correlated with energy utilization. To study metabolic changes at the subcellular level the glucose analogue, 3-OPG was used, which shows a characteristic and intense Raman band at 2124 cm−1.3-OPG was applied as a sensor to track both, its accumulation in live and fixed ECs and then metabolism in normal and inflamed ECs, by employing two spectroscopic techniques, i.e. spontaneous and stimulated Raman scattering microscopies. The results indicate that 3-OPG is a sensitive sensor to follow glucose metabolism, manifested by the Raman band of 1602 cm−1. The 1602 cm−1 band has been called the “Raman spectroscopic signature of life” in the cell literature, and here we demonstrate that it is attributed to glucose metabolites. Additionally, we have shown that glucose metabolism and its uptake are slowed down in the cellular inflammation. We showed that Raman spectroscopy can be classified as metabolomics, and its uniqueness lies in the fact that it allows the analysis of the processes of a single living cell. Gaining further knowledge on metabolic changes in the endothelium, especially in pathological conditions, may help in identifying markers of cellular dysfunction, and more broadly in cell phenotyping, better understanding of the mechanism of disease development and searching for new treatments.

SPECIFICITIES OF TREATMENT OF PATIENTS WITH CARDIOVASCULAR RISK IN COMORBIDITY

Recently, much attention has been paid to the concept introduced to the scientific community by the prominent American epidemiologist Alvan R. Feinstein - "comorbidity" (Latin co - together, morbus - disease). In his understanding, comorbidity demonstrates the combination of two and/or more chronic diseases in one patient, which are interconnected by pathophysiological mechanisms, and simultaneously manifest themselves in one patient, regardless of the degree of activity of each of them. At the same time, comorbidity leads to the formation of new mechanisms of disease development, the unfolding of an additional clinical picture and the addition of complications and courses that are not characteristic of the underlying disease, with a significant negative impact on the quality and duration of life of patiens. Among all patients with comorbidities, patients with cardiovascular risk have been and remain one of the most difficult among all categories of patients. One or other comorbidity can prognostic allylead to a deterioration in the patient's functional state and increase probability of life-threatening risks. Providing proper medical careto patients with comorbidities requires additional economic expenses in the health care system in order to ensure a comprehensive diagnostic procedure and treatment algorithm. To improve the prognosis of patients with comorbidities and reduce the economic burden on the health care system, it is necessary touse a multicomplex approach at the stages of prevention, diagnosis and treatment of major non-communicable diseases that mainly form comorbidity.

Effects of Long-Term Storage on the Biobanked Neonatal Dried Blood Spot Metabolome.

Over 2.5 million neonatal dried blood spots (DBS) are stored at the Danish National Biobank. These samples offer extraordinary possibilities for metabolomics research, including prediction of disease and understanding of underlying molecular mechanisms of disease development. Nevertheless, Danish neonatal DBS have been little explored in metabolomics studies. One question that remains underinvestigated is the long-term stability of the large number of metabolites typically assessed in untargeted metabolomics over long time periods of storage. Here, we investigate temporal trends of metabolites measured in 200 neonatal DBS collected over a time course of 10 years, using an untargeted liquid chromatography tandem mass spectrometry (LC-MS/MS) based metabolomics protocol. We found that a majority (71%) of the metabolome was stable during 10 years of storage at -20 °C. However, we found decreasing trends for lipid-related metabolites, such as glycerophosphocholines and acylcarnitines. A few metabolites, including glutathione and methionine, may be strongly influenced by storage, with changes in metabolite levels up to 0.1-0.2 standard deviation units per year. Our findings indicate that untargeted metabolomics of DBS samples, with long-term storage in biobanks, is suitable for retrospective epidemiological studies. We identify metabolites whose stability in DBS should be closely monitored in future studies of DBS samples with long-term storage.

Pediatric Myeloid Sarcoma, More than Just a Chloroma: A Review of Clinical Presentations, Significance, and Biology.

Myeloid sarcomas (MS), commonly referred to as chloromas, are extramedullary tumors of acute myeloid leukemia (AML) with varying incidence and influence on outcomes. Pediatric MS has both a higher incidence and unique clinical presentation, cytogenetic profile, and set of risk factors compared to adult patients. Optimal treatment remains undefined, yet allogeneic hematopoietic stem cell transplantation (allo-HSCT) and epigenetic reprogramming in children are potential therapies. Importantly, the biology of MS development is poorly understood; however, cell-cell interactions, epigenetic dysregulation, cytokine signaling, and angiogenesis all appear to play key roles. This review describes pediatric-specific MS literature and the current state of knowledge about the biological determinants that drive MS development. While the significance of MS remains controversial, the pediatric experience provides an opportunity to investigate mechanisms of disease development to improve patient outcomes. This brings the hope of better understanding MS as a distinct disease entity deserving directed therapeutic approaches.

Mechanisms of airway disease development following inhalation exposure to indoor fungal contaminants Stachybotrys chartarum and Aspergillus versicolor

Fungi are found ubiquitously in the environment and chronic repeated exposures have been associated with pulmonary and cognitive effects in humans. Previous studies have shown that two prominent indoor fungal contaminants, Stachybotrys chartarum and Aspergillus versicolor, are associated with allergic airway disease, airway remodeling, and Th2-mediated immunological effects. To understand the mechanisms of disease development, genetically modified murine models are an invaluable tool.

Comparative proteomics study of mitochondrial electron transport system modulation in SH-SY5Y cells following MPP+ versus 6-OHDA-induced neurodegeneration

Parkinson’s disease (PD) is the second-most common neurodegenerative disease worldwide. Several studies have investigated PD for decades; however, the exact mechanism of disease development remains unknown. To study PD, SH-SY5Y cells are often treated with 6-hydroxydopamine (6-OHDA) or 1-methyl-4-phenylpyridinium (MPP+) to induce PD. To understand the mechanism of PD pathogenesis, we confirmed protein changes between 6-OHDA- and MPP+-treated SH-SY5Y cells via proteomics analysis using liquid chromatography coupled with tandem mass spectrometry. 6-OHDA-treated SH-SY5Y cells showed increased expression of electron transporter-related proteins compared to that in the control group, along with decreased expression in MPP+-treated SH-SY5Y cells. However, both down- and upregulation of electron transporter-related proteins increased mitochondrial dysfunction and apoptosis. These proteins were confirmed via protein–protein interaction network analysis using IPA and STRING to induce mitochondrial dysfunction and apoptosis. Cell-based experiments using flow cytometry verified that apoptosis and mitochondrial membrane potential were increased in both 6-OHDA- and MPP+-treated SH-SY5Y cells. Our results provide new insights into PD pathogenesis, thereby contributing to the understanding of the mechanisms of PD development.

Хронічна серцева недостатність та остеопороз: етіологічні та клініко-патогенетичні взаємозв’язки

Current epidemiological and clinical data confirm the relationship between chronic heart failure (CHF) and osteoporosis (OP), which cannot be explained only by aging and the use of pharmacological drugs. Clinical and epidemiological studies show that CHF is most often accompanied by low bone mineral density, a high risk of fractures and, moreover, a fourfold increase in the risk of any fracture requiring hospitalization. Further research on the relationship between CHF and OP is needed, as understanding the common mechanisms of disease development will serve as a platform for preventive and therapeutic interventions aimed at both conditions.