Fibrillar Protein Research Articles

Early autoimmunity and outcome in virus encephalitis: a retrospective study based on tissue-based assay

To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses.MethodsA retrospective observational study was conducted...

Histological and electron microscopic features of the extracellular matrix of invasive breast ductal carcinoma of no special type. Report of 5 cases and literature review

ABSTRACT Invasive ductal carcinoma of no special type is the most common type of breast cancer. In light of the above, many authors have reported the histological and electron microscopic characteristics of these tumors. On the other hand, a limited number of works exist where the authors have concentrated on investigating the extracellular matrix. This article presents data received as the results of light and electron microscopic examination of the extracellular matrix, angiogenesis, and cellular microenvironment of invasive breast ductal carcinoma of no special type. The authors have shown that the processes of stroma formation in the IDC NOS type are associated with the presence of fibroblasts, macrophages, dendritic cells, lymphocytes, and other cells. It was also shown the detailed interaction of the above cells with each other, as well as with vessels and fibrillar proteins such as collagen and elastin. The microcirculatory component is characterized by histophysiological heterogeneity, which manifests as the activation of angiogenesis, relative vascular differentiation, and regression of individual microcirculation components.

Identification of New FG-Repeat Nucleoporins with Amyloid Properties.

Amyloids are fibrillar protein aggregates with a cross-β structure. More than two hundred different proteins with amyloid or amyloid-like properties are already known. Functional amyloids with conservative amyloidogenic regions were found in different organisms. Protein aggregation appears to be beneficial for the organism in these cases. Therefore, this property might be conservative for orthologous proteins. The amyloid aggregates of the CPEB protein were suggested to play an important role in the long-term memory formation in Aplysia californica, Drosophila melanogaster, and Mus musculus. Moreover, the FXR1 protein demonstrates amyloid properties among the Vertebrates. A few nucleoporins (e.g., yeast Nup49, Nup100, Nup116, and human Nup153 and Nup58), are supposed or proved to form amyloid fibrils. In this study, we performed wide-scale bioinformatic analysis of nucleoporins with FG-repeats (phenylalanine-glycine repeats). We demonstrated that most of the barrier nucleoporins possess potential amyloidogenic properties. Furthermore, the aggregation-prone properties of several Nsp1 and Nup100 orthologs in bacteria and yeast cells were analyzed. Only two new nucleoporins, Drosophila melanogaster Nup98 and Schizosaccharomyces pombe Nup98, aggregated in different experiments. At the same time, Taeniopygia guttata Nup58 only formed amyloids in bacterial cells. These results rather contradict the hypothesis about the functional aggregation of nucleoporins.

Renal involvement in monogenic autoinflammatory diseases: A narrative review.

Autoinflammatory diseases (AIDs) are mostly caused by dysfunctions in single genes encoding for proteins with a prominent role in the regulation of innate immunity, such as complement factors, inflammasome components, tumour necrosis factor (TNF)-α, and proteins belonging to type I-interferon (IFN) signalling pathways. Due to the deposition of amyloid A (AA) fibrils in the glomeruli, unprovoked inflammation in AIDs frequently affects renal health. In fact, secondary AA amyloidosis is the most common form of amyloidosis in children. It is caused by the extracellular deposition of fibrillar low-molecular weight protein subunits resulting from the degradation and accumulation of serum amyloid A (SAA) in numerous tissues and organs, primarily the kidneys. The molecular mechanisms underlying AA amyloidosis in AIDs are the elevated levels of SAA, produced by the liver in response to pro-inflammatory cytokines, and a genetic predisposition due to specific SAA isoforms. Despite the prevalence of amyloid kidney disease, non-amyloid kidney diseases may also be responsible for chronic renal damage in children with AIDs, albeit with distinct characteristics. Glomerular damage can result in various forms of glomerulonephritis with distinct histologic characteristics and a different underlying pathophysiology. This review aims to describe the potential renal implications in patients with inflammasomopathies, type-I interferonopathies, and other rare AIDs in an effort to improve the clinical course and quality of life in paediatric patients with renal involvement.

Alanine: from the usual to the unexpected

Data from the experiments provides a possibility to talk about anomalously large contribution of alanine to the stability of an alpha-helix and other protein conformations. Independent data (and also experimental ones) suggest that alanine plays an especially big role in stabilization of the alpha-helix. This can be seen through the positive contribution of alanine both to the entropy of the system and to the enthalpy. The high contribution of alanine to the enthalpy of formation of the alpha helix contradicts the generally accepted view that the entropy should decrease during the formation of regular structures in proteins. Among three types of helices in proteins, alanine stabilizes two secondary structures: the alpha helix and the left helix of polyproline II, and in the case of fibrillar proteins, alanine also stabilizes the beta sheet. The stabilizing effect of alanine on the alpha helix structure extends to both natively unfolded proteins and alpha helix-support conjugates. Thus, it is no exaggeration to say that formation of secondary structure relies on alanine. The revealed contradictions are of paradoxical nature and yet there is no interpretation of the above-mentioned findings (first of all, substantiation of the contribution of alanine to the enthalpy of fusion in terms of fundamental physics) so far to resolve them. Meanwhile, the data and comments presented in this work hold out the promise of progress in resolving the revealed contradictions.

Interactions of Fibrillar Proteins with Lipids: A Molecular Docking Insight

The aggregation of misfolded proteins into specific ordered aggregates, amyloid fibrils, associated with more than forty human diseases, currently attracts great research attention in biomedical and nanotechnological aspects. These aggregates and their oligomeric intermediates are thought to exert their toxic action predominantly at the level of cell membranes. In addition, membrane lipids were found in many amyloid deposits in vivo suggesting that lipid molecules are able to incorporate into fibril structure affecting their morphology and mechanical properties. However, the biological implications and structural prerequisites of fibril-lipid interactions still remain unclear. In the present study the molecular docking techniques was employed to explore the interactions between the amyloid fibrils and lipids in the model systems containing the fibrillar forms of lysozyme, insulin, Aβ (1-42) peptide and N-terminal (1-83) fragment of apolipoprotein A-I, as a protein component and cholesterol, cardiolipin or phosphatidylcholine as a lipid component. Using the PatchDock web server and BIOVIA Discovery Studio software, the structural peculiarities of fibril-lipid associates were uncovered. The van der Waals and alkyl/π-alkyl interactions were found to prevail in stabilization of all types of fibril-lipid complexes. The analysis of most energetically favorable docking positions revealed a preferable surface location of lipids and partial penetration of acyl chains of cardiolipin and phosphatidylcholine into fibril grooves.

Evaluation of Microglia Activation Neuroinflammation and Neuronal Loss Presence in Experimentally Generated Rat Autism Model with Propionic Acid

Objective: This study was conducted to determine the behavioral disorders and neuroinflammation that occur in the rat model of autism. Materials and methods: A total of 25 rats, 20 of which were working and 5 were control group, were used in the study. The scores of the rats were recorded by performing a behavioral test before and after the application. A single dose of propionic acid (4 µl, 0.26 M solution) and (4 µl) saline were administered to the brain right ventricles of the rats in the working group and control group, respectively. Hippocampus tissue was obtained after the sacrification process on the 21st day of the rats and examined. Results: Dystrophic changes with small, pycnotic and hyperchromatic nuclei of neurons in the cerebral cortex and hippocampal region were detected in histopathological studies. It was determined that the primitive cell layer thickness of the working group decreased significantly, and their density increased due to irregular chromatolysis in neurons and abnormal Nissl granule distribution. It was determined that the number of glial fibrillar acid protein positive cells increased significantly in the cerebral cortex and hippocampal region in propionic acid applied rats. Conclusion: Propionic acid crosses the blood brain barrier. As a result, neuroinflammation, microglial activation and loss of myelin are observed in the brain.

Search and Identification of Amyloid Proteins

Amyloids are fibrillar proteins with a cross-β structure. Pathological amyloids are associated with the development of a number of incurable diseases, while functional amyloids regulate vital processes. The detection of unknown amyloids in living objects is a difficult task, and therefore the question of the prevalence and biological significance of amyloids remains open. We present a description of two methods, the combination of which makes it possible to find and identify amyloid proteins in the proteome of various organisms. The method of proteomic screening for amyloids allows the detection of the proteins that form SDS-resistant aggregates. SDS resistance is a general feature of amyloid fibrils. Protein aggregates resistant to SDS treatment can be collected by ultracentrifugation and further identified by mass spectrometry. However, in addition to amyloids, SDS-resistant aggregates contain some non-amyloid proteins. To test the amyloid properties of proteins identified by proteomic screening, we developed the method of fibril immunoprecipitation followed by Congo red staining and birefringence analysis. The methods of proteomic screening and immunoprecipitation of fibrillar proteins have been successfully tested and applied for the identification of amyloid proteins in yeast and vertebrates.

Intraoperative transfusion is a risk factor for cerebral injury after cardiac surgery in children: a prospective observational study

INTRODUCTION: Donor blood components are able to initiate a systemic inflammatory response syndrome (SIRS) and potentiate neuroinflammation with subsequent cerebral damage. OBJECTIVE: To study the effect of transfusion on the development of cerebral damage during the surgical correction of congenital heart defects in children. MATERIALS AND METHODS: 78 patients aged from 1 to 78 months, weighing from 3.3 to 21.5 kg, were studied. All patients underwent correction of a septal defect under cardiopulmonary bypass. All patients were divided to group 1 — without the use of transfusion and group 2 — with the use of red blood cell transfusion. Cerebral damage markers (S-100-β protein, neuron-specific enolase (NSE) and glial fibrillar acidic protein (GFAP)) and SIRS (interleukins 1 (ILb-1), 6 (IL-6), 10 (IL-10) and tumor necrosis factor alpha (TNF-α) were studied. Markers ware studied at three control points: 1 — before the start of surgery, 2 — immediately after end of cardiopulmonary bypass, 3 — 16 hours after the end of the operation. RESULTS: The peak concentration of most markers in the blood in both groups of patients was noted at the 2nd control point. The concentration of all markers of cerebral damage was significantly higher in the transfusion group at the 2nd control point: S-100-β protein (ng/ml) — 509.90 [379.30–871.70] and 717.10 [517.90–1195.33] (р = 0.024); NSE (ng/ml) — 17.55 [11.19–26.41] and 34.05 [17.06–44.90] (р = 0,023); GFAP (ng/ml) — 0.1190 [0.1135–0.1245] and 0.1231 [0.1138–0.1493]. Correlations were found between markers of cerebral damage and SIRS, the strongest of which was the relationship between NSE and TNF-α at the 3rd control point — Rho = 0.43 (p = 0.0001). A correlation of S-100-β protein with transfusion volume was observed at the 2nd (Rho = 0.48, p = 0.00065) and 3rd control points (Rho = 0.36, p = 0.01330). CONCLUSIONS: The influence of the fact of transfusion and the dose of red blood cell on the development of cerebral damage during cardiac surgery in children has been proven.

Selective In Vitro and Ex Vivo Staining of Brain Neurofibrillary Tangles and Amyloid Plaques by Novel Ethylene Ethynylene-Based Optical Sensors.

The identification of protein aggregates as biomarkers for neurodegeneration is an area of interest for disease diagnosis and treatment development. In this work, we present novel super luminescent conjugated polyelectrolyte molecules as ex vivo sensors for tau-paired helical filaments (PHFs) and amyloid-β (Aβ) plaques. We evaluated the use of two oligo-p-phenylene ethynylenes (OPEs), anionic OPE12- and cationic OPE24+, as stains for fibrillar protein pathology in brain sections of transgenic mouse (rTg4510) and rat (TgF344-AD) models of Alzheimer's disease (AD) tauopathy, and post-mortem brain sections from human frontotemporal dementia (FTD). OPE12- displayed selectivity for PHFs in fluorimetry assays and strong staining of neurofibrillary tangles (NFTs) in mouse and human brain tissue sections, while OPE24+ stained both NFTs and Aβ plaques. Both OPEs stained the brain sections with limited background or non-specific staining. This novel family of sensors outperformed the gold-standard dye Thioflavin T in sensing capacities and co-stained with conventional phosphorylated tau (AT180) and Aβ (4G8) antibodies. As the OPEs readily bind protein amyloids in vitro and ex vivo, they are selective and rapid tools for identifying proteopathic inclusions relevant to AD. Such OPEs can be useful in understanding pathogenesis and in creating in vivo diagnostically relevant detection tools for neurodegenerative diseases.

Probing the Interactions of LRP1 Ectodomain-Derived Peptides with Fibrillar Tau Protein and Its Impact on Cellular Internalization

Cellular internalization and the spreading of misfolded tau have become increasingly important for elucidating the mechanism of Tau pathology involved in Alzheimer’s disease (AD). The low-density lipoprotein-related receptor 1 (LRP1) has been implicated in the internalization of fibrillar tau. In this work, we utilized homology modeling to model the Cluster 2 domain of LRP1 and determined that a 23-amino-acid sequence is involved in binding to paired helical filaments (PHF) of Tau. Fourteen short peptide segments derived from this ectodomain region were then designed and docked with PHF Tau. Molecular dynamics studies of the optimal peptides bound to PHF Tau demonstrated that the peptides formed critical contacts through Lys and Gln residues with Tau. Based on the computational results, flow cytometry, AFM, SPR analysis and CD studies were conducted to examine binding and cellular internalization. The results showed that the peptide sequence TauRP (1–14) (DNSDEENCES) was not only associated with fibrillar Tau but was also able to mitigate its cellular internalization in LRP1-expressed HEK-293 cells. Preliminary docking studies with Aβ (1–42) revealed that the peptides also bound to Aβ (1–42). While this study focused on the CCR2 domain of LRP1 to design peptide sequences to mitigate Tau internalization, the work can be extended to other domains of the LRP1 receptor or other receptors to examine if the cellular internalization of fibrillar Tau can be deterred. These findings show that short peptides derived from the LRP1 receptor can alter the internalization of its ligands.

Chapter 14 - Motor symptoms in nonparaneoplastic CNS disorders associated with neural antibodies

Motor symptoms are common, and sometimes predominant, in almost all nonparaneoplastic CNS disorders associated with neural antibodies. These CNS disorders can be classified into five groups: (1) Autoimmune encephalitis with antibodies against synaptic receptors, (2) cerebellar ataxias associated with neuronal antibodies that mostly target intracellular antigens. (3) Stiff-person syndrome and progressive encephalomyelitis with rigidity and myoclonus which have antibodies against glutamic acid decarboxylase and glycine receptor, respectively. Both diseases have in common the presence of predominant muscle stiffness and rigidity. (4) Three diseases associated with glial antibodies. Two present motor symptoms mainly due to the involvement of the spinal cord: neuromyelitis optica spectrum disorders with aquaporin-4 antibodies and myelin oligodendrocyte glycoprotein antibody-associated disease. The third disorder is the meningoencephalitis associated with glial fibrillar acidic protein antibodies which frequently also presents a myelopathy. (5) Two antibody-related diseases which are characterized by prominent sleep dysfunction: anti-IgLON5 disease, a disorder that frequently presents a variety of movement disorders, and Morvan syndrome associated with contactin-associated protein-like 2 antibodies and clinical manifestations of peripheral nerve hyperexcitability. In this chapter, we describe the main clinical features of these five groups with particular emphasis on the presence, frequency, and types of motor symptoms.

Coherence of the electroencephalogram and peripheral markers of nerve tissue damage in depressive disorders

To evaluate the coherence parameters of the electroencephalogram and the level of peripheral markers of nerve tissue damage in patients with depressive disorders. Thirty patients with a diagnosis from a cluster of mood disorders: affective disorder within a single depressive episode and recurrent depressive disorder were examined. A control group consisted of 30 healthy individuals, comparable in sex and age to the main group. The bioelectric activity of the brain was recorded and analyzed with the calculation of the averaged coefficients of intra- and interhemispheric coherence. The concentration of calcium-binding protein S100b, the main protein of myelin MBP and glial fibrillar acid protein GFAP was determined in blood sera by solid-phase enzyme immunoassay. Patients with depressive disorders showed signi cantly lower coefficients of interhemispheric coherence of alpha (p=0.003), beta (p=0.042) and theta rhythms (p=0.041), as well as intrahemispheric coherence of alpha rhythm in the left (p=0.016) and right hemispheres (p=0.026), beta rhythm in the right hemisphere (p=0.034) compared to the control group. Patients with depressive disorders showed a higher concentration of MBP compared to the control group (p=0.008). Additionally, we identified statistically significant correlations between EEG coherence coefficients and serum markers in patients with depressive disorders. The results clearly confirm the presence of inflammatory changes in the brain in patients with depression, which is reflected in structural and functional changes.

Clinical characteristics and short-term outcomes of autoimmune encephalitis in adults

To characterize clinical, paraclinical features and short-term outcomes in different types of autoimmune encephalitis (AE) in a one-center cohort of Russian patients, as well as to evaluate the frequency and significance of the joint expression of antineuronal and anti-glial antibodies (Abs) in AE. Forty-one patients were diagnosed with AE at the Research Center of Neurology from November 2020 to December 2022. Demographic, clinical characteristics, results of laboratory tests, MRI of brain, treatment and outcomes of disease were analyzed. The analysis of Abs to glial antigens (myelin-oligodendrocyte glycoprotein - MOG, glial fibrillar acidic protein - GFAP, aquaporin 4 - AQP-4) was performed by indirect immunofluorescence assay (Euroimmun, Germany). In 24 (58.5%) patients was established definite AE, confirmed by specific Abs detection; in 2 (4.9%) - definite limbic encephalitis, in 15 (36.6%) - seronegative probable AE (including 3 cases of Hashimoto's encephalitis). GFAP-Abs in cerebrospinal fluid (CSF) were detected only in two patients - with clinical and MRI-picture of autoimmune GFAP-astrocytopathy (A-GFAP-A). GFAP- and MOG-Abs in the blood were detected in 25.7% and 6%, respectively, AQP-4-Abs were not detected. There were no correlations between co-expression with glial Abs and clinical characteristics. Systemic and antithyroid Abs were present in 15% and 31%, respectively. Paraneoplastic AE accounted for 22%. For the first time in the Russian population, 2 cases of A-GFAP-A, 6 cases of AE associated with COVID-19 were described. The most common first syndrome were epileptic seizure (34%), psychiatric (29%) and cognitive (14%) disorders. Relapses of AE was observed in 22%. Inflammatory changes in CSF were detected in 41%, focal changes on MRI in 68%. First-line immune therapy was performed in all patients, 85% of cases received pulse therapy with methylprednisolone. Second-line immune therapy (rituximab or cyclophosphamide intravenously) was performed in 19.5%, 78% of patients achieved significant improvement during treatment (scores ≤2 on the modified Rankin scale). The results allow us to consider COVID-19 as a trigger of AE. The absence of detection of GFAP-Abs in CSF in patients with other types of AE contributes to the confirmation of the specificity of GFAP-seropositivity of CSF for the diagnosis of A-GFAP-A. The expression of GFAP- and MOG-Abs in AE can serve as confirmation of the immuno-mediated etiology of the disease, which is especially important for the AE diagnosis in the absence of antineuronal Abs.

Neurospecific Proteins as Transdiagnostic Markers of Affective Disorders

Mental disorders have many differences in pathogenesis and clinical symptoms, however, they are characterized by general neurobiological processes that occur with a damage of nervous tissue, disturbance of blood-brain barrier, inclusion of autoimmune mechanisms, neurodegenerative processes and release of neurospecific proteins into the liquor and into the blood. We presented a review of current literature devoted to studies of the role of neurospecific proteins in the pathogenesis of affective disorders. Glial fibrillar acidic protein (GFAP), S-100 protein, myelin basic protein (MBP), and neuron specific enolase (NSE) reflect damage of neurons, astrocytes and oligodendrocytes in depressive disorders and they could be considered as transdiagnostic nonspecific markers of affective disorders.

ЛАБОРАТОРНЫЕ БИОМАРКЁРЫ ПОВРЕЖДЕНИЯ ГОЛОВНОГО МОЗГА ПРИ САХАРНОМ ДИАБЕТЕ

Objective: This review outlines the literature data on the main laboratory biomarkers of brain damage in diabetes mellitus (DM) type I and II. Neurospecific proteins: S-100 protein, neurospecific enolase, glial fibrillar acidic protein, myelin basic protein, and brain-derived neurotrophic factor (BDNF) are considered specific markers of cerebral dysfunction in DM. Emphasis is placed on pro-inflammatory cytokines (IL-1, IL-6, tumor necrosis factor-α, C-reactive protein), as blood biomarkers, the increase of which indicates brain damage in DM type I and II. High concentrations of adipokines, inflammatory mediators of adipose tissue, are a reliable laboratory sign of brain damage in this endocrinopathy. Advanced glycation end products (AGEs), as pathogenic metabolites of oxidative stress (OS), detected in blood in high concentration, can act as indicators of cognitive deficit in DM. Increased concentration of autoantibodies to some neuroreceptors (dopamine, glutamate) may serve as specific laboratory biomarkers of brain damage in DM type I. Further searches of new laboratory biomarkers of brain dysfunction are needed in order to improve the diagnosis of cerebral insufficiency in DM Keywords: Diabetes mellitus, biomarkers, brain damage, neurospecific proteins, adipokines.

Newly identified transmembrane protein 106B amyloid fibrils in the human brain: pathogens or by-products?

Neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) constitute a spectrum of diseases characterized by the abnormal aggregation of specific amyloid fibrillar proteins; these include β-amyloid (Aβ) and tau in the form of the extracellular Aβ plaques and neuronal neurofibrillary tangles in AD and fibrillar α-synuclein aggregation in the form of Lewy bodies and Lewy neurites in PD. Transmembrane protein 106B (TMEM106B) is a type II transmembrane lysosomal protein that participates in lysosome morphology, localization, acidification, and trafficking; t is involved in the pathogenesis of several NDs, especially frontotemporal lobular degeneration with TAR DNA-binding protein immunoreactive inclusions (FTLD-TDP). Studies from four independent research groups revealed that the luminal domain of TMEM106B (120-254aa) forms amyloid fibrils in several brain regions in patients with a series of NDs and neurologically normal older adults. Given its potentially critical roles in the pathogenesis of NDs and brain aging, this surprising finding has focused attention on TMEM106B and suggested that it is nearly as fundamental as other pathogenic amyloid proteins (e.g., Aβ, tau, α-syn); nevertheless, new questions surrounding TMEM106B must be asked. In this review,we firstly introduce the physiological function of TMEM106B and its involvement in NDs. Then, we elucidate the identification and cryo-electronic microscopic structure of TMEM106B fibrils and analyze the factors that contribute to the polymorphism of TMEM106B fibrils. Finally, the potential pathogenic role of TMEM106B fibrils is discussed, and the future directions for TMEM106 research in NDs are briefly summarized.

Regulation of Collagen I and Collagen III in Tissue Injury and Regeneration.

The structure of connective tissues including cartilage, tendons, and ligaments as well as many organs, like the skin, heart, liver, kidney, lungs, blood vessels, and bones, depend on collagen. The bulk of the network of structural proteins that make up the extracellular matrix of the heart is composed of collagen type I and type III, which provide structural support for the muscle cells and are crucial for cardiac function. The prognosis and progression of a disease or diseased state may be significantly impacted by the upregulation or downregulation of the collagen types, particularly Col I and Col III. For example, increasing Col I protein levels may impose increasing myocardial stiffness, impairing the diastolic and systolic function of the myocardium. Collagen I is a stiff fibrillar protein that gives tensile strength, whereas Col III produces an elastic network that stores kinetic energy as an elastic rebound. These two collagen proteins have distinct physical properties in nature. Therefore, the control of Col I and Col III as well as the potential relevance of the Col I/Col III ratio in many biological processes serve as the foundation for this comprehensive review article.

Computer simulation of the wound process (review of literature)

Relevance. Computer simulation is a mathematical modeling process performed on a computer that is designed to predict the behavior or results of a real or physical system. Computer simulation has a number of advantages over classical models of animal experiments: the cheapness of the method (the need to acquire and maintain animals disappears by itself), the speed of obtaining results, the absence of bioethical problems, the ability to change the conditions of the experiment, etc.he purpose of this study is to review the methods of computer simulation of the wound process, to identify the shortcomings of the models and propose ways to solve them, as well as to select the best existing model for describing wound regeneration.Material and methods. In the course of this work, an analysis was made of foreign and domestic literature on the problem of computer modeling of the wound process.Results. After analyzing the relevant literature on this topic, the problem is seen precisely in the insufficiently studied process of wound regeneration, since many different cells, cytokines, growth factors, enzymes, fibrillar proteins, etc. take part in it. The models that currently exist describe wound regeneration only in an extremely generalized way, which does not allow us to apply them in clinical situations. Analyzing literature sources, we came to the conclusion that both numerical approaches, both cellular-biochemical (the first type of models) and phenomenological (the second type) are applicable in the case of wound modeling and can be used very successfully. The problem is that on the basis of one approach it is impossible to display a complete picture of wound healing, in this way it is possible to predict only individual regeneration parameters necessary for certain purposes due to the complexity and versatility of this typical pathophysiological process.Conclusion. Computer modeling of wounds is still a controversial and complex topic. Existing models are not intended to describe all the processes occurring in a healing wound. It is much more productive to describe the various phenomena during healing separately. This is due to the fact that many elements are involved in the regeneration of the skin, which are almost impossible to take into account in full. The available models are of exclusively scientific value, consisting in attempts to understand all complex processes and interactions. Practical application is difficult, since existing models require specific input data that require highly specialized equipment. If we abstract from all this, then the best existing model of the first type is the model of the authors Yangyang Wang, Christian F. Guerrero-Juarez, Yuchi Qiu and co-authors, in addition to it, any of the described phenomenological models will do.

A rare case of systemic AL-amyloidosis under the mask of myocardial infarction in the absence of myocardial hypertrophy: case report

Systemic amyloidosis is a group of diseases associated with extracellular deposition of fibrillar proteins, resulting in the loss of normal organ structure and function. AL-amyloidosis occurs when amyloid is deposited, consisting of full-length lambda or kappa immunoglobulin light chains, or fragments thereof. This article describes the complexity of timely diagnosis of systemic AL-amyloidosis with a predominant heart lesion in the absence of myocardial hypertrophy on the example of an elderly patient in whom the leading manifestation of the disease was heart failure with a preserved left ventricular ejection fraction.