Pathophysiological Reactions Research Articles

Extracellular vesicles in burn injury: roles, mechanisms, and applications

Abstract Burn injuries are associated with high morbidity and mortality, and severe burns trigger many pathophysiological reactions, such as metabolic changes, distributive shock, and inflammatory responses, which are potentially devastating to patients. Burn wound management necessitates infection prevention, anti-inflammation, pain management, and growth factor management, but significant obstacles remain. Extracellular vesicles (EVs) are lipid bilayer vesicles secreted by various cell types, including mammalian cells, plant cells, and even prokaryotes, They are widely involved in various biological processes, such as cell survival, neovascularization, and immunomodulation. EVs are abundant in components that can play a significant role in different stages of wound repair and at different subcellular levels simultaneously by transporting various active contents, such as proteins and nucleic acids. Moreover, EVs are detectable in many biofluids of burn injury patients and are thus regarded as novel biomarkers for monitoring therapeutic response and predicting prognosis. This review summarizes the biological roles of EVs and their mechanisms of action in burn injury are summarized. The prospects and opportunities for the clinical application of EVs in burn wounds are also discussed. This review will stimulate and guide additional in-depth studies of EVs in burn wound repair, provide a new therapy for burn wounds, and provide a reference and guidance for applying EVs in clinical wound repair.

Phillyrin and its metabolites exert antipyretic effects by targeting the NAD+ binding domain of GAPDH, MDH2 and IDH2

BackgroundFever is one of the main pathophysiological reactions that occurs during the acute phase of various diseases. Excessive body temperature can lead to various adverse consequences such as brain tissue damage and abnormal immune responses. Phillyrin (Phr) is the main active ingredient in Forsythia suspensa (Thunb.) Vahl (Lian Qiao) and has antipyretic effects; however, its antipyretic mechanism of action remains unclear. PurposeThis study aimed to explore the antipyretic mechanisms of Phr and provide a new treatment plan for fever. MethodsThe antipyretic effects of Phr were evaluated using a mouse model of pneumonia fever. The main metabolites of Phr involved in its antipyretic function were identified using a mitochondrial temperature-sensitive probe. Further synthesis of the main metabolite, phillygenin (Phg), an alkynylated probe, was performed, and chemical proteomics was used to capture and analyze its direct target for antipyretic effects. The mechanism of action of Phg and its antipyretic targets was explored using metabolomics and various molecular biology methods. ResultsPhr showed significant antipyretic and anti-inflammatory effects in a mouse model of lipopolysaccharide-induced fever. Phg reversibly targeted the nicotinamide adenine dinucleotide (NAD+) binding domain of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), malate dehydrogenase 2 (MDH2), and isocitrate dehydrogenase 2 (IDH2) to inhibit their enzymatic activity. In-depth analysis of cellular metabolomics and mitochondrial stress testing indicated that inhibition of GAPDH, MDH2, and IDH2 enzyme activity by Phg led to a decrease in cellular energy supply and heat production regulated by glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation signaling pathways. Phg specifically targeted macrophages and inhibited LPS-induced macrophage activation by downregulating GAPDH enzyme activity, thereby exerting anti-inflammatory effects. In vivo experiments also confirmed that the antipyretic effect of Phr in LPS-induced fever model mice was related to its main metabolites, Phg and Phg-sulfonate (Phg-S), which directly targeted the NAD+ binding domain of GAPDH, IDH2, and MDH2, inhibiting the activity of these enzymes, thereby reducing energy supply and regulating febrile-related inflammatory factors. ConclusionThis study reported for the first time that the antipyretic effect of Phr is produced by targeting GAPDH, IDH2, and MDH2 to regulate energy supply and febrile-related inflammatory factors through its main metabolites Phg and Phg-S. This study not only provides potential drugs for fever treatment but also provides new ideas for improving clinical fever treatment plans.

Severe Thoracic Trauma Indications and Contraindications for Non-operative and Operative Treatment Strategies

Severe thoracic trauma can occur as a penetrating or blunt mono-injury or as part of a polytrauma. Almost half of all severely injured patients documented in the TraumaRegister DGU were diagnosed with severe chest trauma, defined according to the Abbreviated Injury Scale (AIS) as ≥3. In our own collective, the proportion was even higher with 60%. Emergency surgical treatment with a thoracotomy within the Trauma Resuscitation Unit or within the first hour of admission is an extremely rare intervention in Germany, accounting for 0.9% of severe thoracic injuries. The management of complex polytraumas and extensive pathophysiological reactions to the trauma, as well as knowledge about the development of secondary damage have led to the conclusion that minimally invasive procedures such as video-assisted thoracoscopy (VATS) or inserting a chest drain can resolve most severe thoracic injuries. At <4%, penetrating injuries to the thorax are a rarity. Among blunt thoracic injuries, >6% show an unstable thoracic wall that requires surgical reconstruction. The demographic development in Germany leads to a shift in injury pattern. Low-energy trauma results have lower incidence than higher-grade chest wall injuries with penetrating rib fractures in the pleura, lungs, peri-/myocardium and diaphragm. Sometimes this results in instability of the chest wall with severe restriction of respiratory mechanics, which leads to fulminant pneumonia and even ARDS (Acute Respiratory Distress Syndrome). With this background, surgical chest wall reconstruction has become increasingly important over the past decade. Together with the underlying strong evidence, the assessment of the extend and severity of the trauma and the degree of respiratory impairment are the basis for a structured decision on a non-surgical or surgical-reconstructive strategy, as well as the timing, type and extent of surgery. Early surgery within 72 hours can reduce morbidity (pneumonia rate, duration of intensive care and ventilation) and mortality. In the following article, evidence-based algorithms for surgical and non-operative strategies are discussed in the context on the management of severe thoracic injuries. Thus, a selective literature search was carried out for the leading publications on indications, treatment strategy and therapy recommendations for severe thoracic injury, chest wall reconstruction.

Endothelial-mesenchymal transition, ventricular remodeling after myocardial infarction, and research progress of Chinese medicine intervention

Ventricular remodeling after myocardial infarction(VRAMI) is a pathological phenomenon triggered by the abrupt occlusion of coronary arteries, leading to myocardial ischemia and hypoxia. This intricate process encompasses alterations in the dimensions, composition, and elasticity of the ventricular tissue and reflects pathophysiological reactions and self-repair after cardiomyocytes are damaged. The characteristic pathological manifestation of VRAMI is the presence of myocardial fibrosis(MF), wherein fibrotic cardiac tissue undergoes a loss of contractile and relaxation capacity, ultimately culminating in heart failure(HF) and significantly impacting the patient's prognosis. Endothelial-mesenchymal transition(EndMT) is a biological process in which endothelial cells, in response to diverse pathological stimuli such as ischemia and hypoxia in the embryonic development period, undergo morphological alterations and functional impairment, progressively acquiring mesenchymal cell properties and ultimately differentiating into mesenchymal cells. The ongoing advancement of the EndMT process will result in an excessive buildup of collagen, thereby inducing structural harm to the myocardium and exacerbating the processes of VRAMI and MF. Recent investigations have demonstrated the pivotal involvement of EndMT in the pathological advancement of VRAMI. Consequently, a targeted intervention aimed at effectively impeding VRAMI, safeguarding cardiac function, and potentially serving as a novel therapeutic target for the prevention and treatment of VRAMI. This article provides a comprehensive review of recent Chinese and international literature, focusing on the role and pathophysiological mechanisms of EndMT in VRAMI. Additionally, it discusses the research progress of innovative targeted interventions using both traditional Chinese and Western medicine, so as to offer new insights and a theoretical foundation for the clinical treatment of the disease.

Pulmonary hypertension associated with congenital portosystemic shunts as a new form of portopulmonary hypertension in children and adults

Pulmonary arterial hypertension (PAH) associated with portal hypertension, or portopulmonary hypertension, is a severe, life-threatening complication of portal hypertension and/or portocaval shunt surgery. Congenital portocaval shunts (CPSSs) are rare vascular anomalies of the portal system, leading to severe pathophysiological reactions and multisystem damage, including PAH, liver nodules, cognitive, metabolic, immune, hematological and hormonal disorders. Severe cardiopulmonary complications are detected in more than a third of patients with CPSSs, which is the main cause of their death. The article describes the pathophysiology, clinical characteristics, diagnostic features and possibilities of modern targeted therapy for CPSS-associated PAH. Patients with CPSS-associated PAH require comprehensive specialized care in an expert center. For long-term successful management of patients, continuous targeted therapy for PAH, in combination with surgical treatment of CPSSs, is crucial.

Cerebral Hypoxia During Intermittent Hypoxic-Hyperoxic Training (IHHT): A Case Study Using Cerebral Oximetry Based on Time-Domain Near-Infrared Spectroscopy.

In intermittent hypoxia-hyperoxia training (IHHT), air is inhaled through a mask, with the O2 content of the air varying at intervals. IHHT is used in sports training (e.g. to improve exercise tolerance), but also in medical-therapeutic applications (e.g. to improve cognitive performance and functional exercise capacity in geriatric patients). We aimed to evaluate the ability of a novel time-domain near-infrared spectroscopy (TD-NIRS) device to measure the effects of IHHT on cerebrovascular oxygenation and haemodynamics. One subject (41years old, male, athlete, colleague of the authors) performed an IHHT session as part of his regular training. In parallel, systemic physiological activity (arterial oxygenation (SpO2) and pulse rate (PR)) as well as cerebrovascular oxygenation (StO2) and haemodynamics (total haemoglobin concentration, [tHb]) were measured. For the measurement of StO2 and [tHb], a TD-NIRS device (NIRSBOX, PIONIRS, Italy) was employed. The TD-NIRS device uses two diode lasers (685 nm and 830nm) as light sources and a solid-state light detector. The optode of the TD-NIRS device was placed over the left prefrontal cortex of the subject. The IHHT session had a total duration of 32minutes and consisted of four cycles of hypoxia (5min, O2: 10%) followed by hyperoxia (3min, O2: 34%). The IHHT session caused significant changes in SpO2, HR, StO2 and [tHb]. The hypoxia/hyperoxia challenges resulted in a decrease in SpO2 from 97% to ~70% and decrease in StO2 from ~70 to ~60%. During the hypoxia intervals, HR increased from ~50 to ~60, while [tHb] increased only moderately (from ~64 to ~66μM). The case study presented here demonstrates the feasibility of the novel TD-NIRS device to measure changes in cerebrovascular haemodynamics and oxygenation during an IHHT session. It was observed that an intense IHHT session causes significant cerebral hypoxia (decrease of StO2 by 10 percentage points). In contrast, cerebral haemodynamics (as indicated by changes in [tHb]) were only weakly influenced. Our study shows that IHHT can have a significant effect on the oxygen supply in the head, which should be taken into account in future applications of IHHT to prevent possible pathophysiological reactions that could be triggered by it.

Gut microbiota in relationship to diabetes mellitus and its late complications with a focus on diabetic foot syndrome: A review.

Diabetes mellitus is a chronic disease affecting glucose metabolism. The pathophysiological reactions underpinning the disease can lead to the development of late diabetes complications. The gut microbiota plays important roles in weight regulation and the maintenance of a healthy digestive system. Obesity, diabetes mellitus, diabetic retinopathy, diabetic nephropathy and diabetic neuropathy are all associated with a microbial imbalance in the gut. Modern technical equipment and advanced diagnostic procedures, including xmolecular methods, are commonly used to detect both quantitative and qualitative changes in the gut microbiota. This review summarises collective knowledge on the role of the gut microbiota in both types of diabetes mellitus and their late complications, with a particular focus on diabetic foot syndrome.

Features of the course of traumatic shock when using respiratory mixtures with a high content of inert gases

This study evaluated the efficiency of using gas mixtures with increased concentrations of inert gases on a hemorrhagic shock model in experimental animals. Massive blood loss is considered a trigger mechanism of severe pathophysiological reactions (impaired peripheral perfusion, acidosis, hemostasis system dysfunction, and multiple organ failure). Inert gases (helium, argon, and xenon) attract attention as potentially useful in various pathological conditions. The study was conducted on 15 same-sex pigs of the same breed, weighing 40–50 kg, randomized into three groups with five each: control group, inhalation of 100% oxygen; “agohhep” group, inhalation of the “Aroxxen” gas mixture: 35% argon, 58% oxygen, 0.2% xenon, and nitrogen as the rest of the volume; and “agohhep-krypto” group, inhalation of the gas mixture “Aroxxen-krypto”: 35% argon, 40% oxygen, 10% krypton, and nitrogen as the rest of the volume. Dynamic monitoring of vital signs and sampling of materials were conducted before blood loss, with blood loss of 20% and 45% of the volume of the circulating blood 60, 120, and 180 min after blood loss. The survival rate of animals and respiratory and circulatory states were evaluated by clinical and laboratory indicators. With blood loss of 45% of the circulating blood volume, no statistically significant differences in mortality were found between the groups. All animals survived for 180 min in the post-hemorrhagic period. In the aggohep-krypto group, average blood pressure values after blood loss and throughout the follow-up period were significantly higher than those in the control and aggohep groups (p 0.05). During shock simulation as a result of blood loss, base deficiency gradually worsened in all groups. However, starting from the second hour of observation, base deficiency began to be compensated in the control and aggohep-krypto groups and the aggohep group, it continued to increase significantly (p 0.01). During the follow-up after blood loss, the level of lactatemia significantly increased in the aggohep group (by 10 times at the end of the follow-up), which is significant different from those in the control and aggohep-krypto groups (p 0.01). Thus, compared with the use of Arroxen gas, the use of Arroxen-krypto gas of the proposed composition in acute massive blood loss makes it possible to achieve a less pronounced attrition of the acid–base balance in experimental animals.

Transcription factor EB: A potential integrated network regulator in metabolic-associated cardiac injury.

With the worldwide pandemic of metabolic diseases, such as obesity, diabetes, and non-alcoholic fatty liver disease (NAFLD), cardiometabolic disease (CMD) has become a significant cause of death in humans. However, the pathophysiology of metabolic-associated cardiac injury is complex and not completely clear, and it is important to explore new strategies and targets for the treatment of CMD. A series of pathophysiological disturbances caused by metabolic disorders, such as insulin resistance (IR), hyperglycemia, hyperlipidemia, mitochondrial dysfunction, oxidative stress, inflammation, endoplasmic reticulum stress (ERS), autophagy dysfunction, calcium homeostasis imbalance, and endothelial dysfunction, may be related to the incidence and development of CMD. Transcription Factor EB (TFEB), as a transcription factor, has been extensively studied for its role in regulating lysosomal biogenesis and autophagy. Recently, the regulatory role of TFEB in other biological processes, including the regulation of glucose homeostasis, lipid metabolism, etc. has been gradually revealed. In this review, we will focus on the relationship between TFEB and IR, lipid metabolism, endothelial dysfunction, oxidative stress, inflammation, ERS, calcium homeostasis, autophagy, and mitochondrial quality control (MQC) and the potential regulatory mechanisms among them, to provide a comprehensive summary for TFEB as a potential new therapeutic target for CMD.

Ferroptosis: a potential therapeutic target for stroke.

Ferroptosis is a form of regulated cell death characterized by massive iron accumulation and iron-dependent lipid peroxidation, differing from apoptosis, necroptosis, and autophagy in several aspects. Ferroptosis is regarded as a critical mechanism of a series of pathophysiological reactions after stroke because of iron overload caused by hemoglobin degradation and iron metabolism imbalance. In this review, we discuss ferroptosis-related metabolisms, important molecules directly or indirectly targeting iron metabolism and lipid peroxidation, and transcriptional regulation of ferroptosis, revealing the role of ferroptosis in the progression of stroke. We present updated progress in the intervention of ferroptosis as therapeutic strategies for stroke in vivo and in vitro and summarize the effects of ferroptosis inhibitors on stroke. Our review facilitates further understanding of ferroptosis pathogenesis in stroke, proposes new targets for the treatment of stroke, and suggests that more efforts should be made to investigate the mechanism of ferroptosis in stroke.

Когнитивные нарушения при хронической цереброваскулярной патологии и возможности их коррекции на додементных стадиях

Cerebrovascular diseases are among the most frequent nosological forms of modern neurology. One of the most important components of their clinical picture is cognitive impairment. At the same time, the most frequent is the development of mild and moderate cognitive disorders. This is especially true for the initial stages of the disease. The pathogenetic basis of the violation of higher cortical functions is a complex of pathophysiological and pathochemical reactions formed within the cascade of ischemic damage to the brain substance. One of the central places among them is occupied by the development of energy deficiency due to a decrease in ATP synthesis and the formation of oxidative stress. This makes it necessary to prescribe pharmacological drugs that can have a multimodal effect. Among such drugs, idebenone is distinguished, which can stimulate the mitochondrial respiratory chain and, in addition, exhibits antioxidant properties. which has demonstrated its effectiveness in the treatment of pre-segment cognitive impairment in patients with cerebrovascular pathology, especially in the framework of combined administration with drugs having other mechanisms of action.

Perspectives on oral chronic graft-versus-host disease from immunobiology to morbid diagnoses.

Chronic Graft-versus-Host Disease (cGVHD) is a major long-term complication, associated with morbidity and mortality in patients following allogenic hematopoietic cell transplantation (HCT) for immune hematopoietic disorders. The mouth is one of the most frequently affected organs after HCT (45-83%) and oral cGVHD, which may appear as the first visible sign. Manifestations present with mucosal lichenoid lesions, salivary gland dysfunction and limited oral aperture. Diagnosis of oral cGVHD severity is based on mucosal lesions with symptoms of sensitivity and pain and reduced oral intake. However, diagnostic difficulties arise due to subjective definitions and low specificity to cover the spectrum of oral cGVHD. In recent years there have been significant improvements in our understanding of the underlying oral cGVHD disease mechanisms. Drawing upon the current knowledge on the pathophysiology and biological phases of oral cGVHD, we address oral mucosa lichenoid and Sjogren's Syndrome-like sicca syndromes. We consider the response of alloreactive T-cells and macrophages to recipient tissues to drive the pathophysiological reactions and biological phases of acute inflammation (phase 1), chronic inflammation and dysregulated immunity (phase 2), and subsequent aberrant fibrotic healing (phase 3), which in time may be associated with an increased malignant transformation rate. When formulating treatment strategies, the pathophysiological spectrum of cGVHD is patient dependent and not every patient may progress chronologically through the biological stages. As such there remains a need to address and clarify personalized diagnostics and management to improve treatment descriptions. Within this review, we highlight the current state of the art knowledge on oral cGVHD pathophysiology and biological phases. We address knowledge gaps of oral cGVHD, with a view to facilitate clinical management and improve research quality on lichenoid biology and morbid forms of oral cGVHD.

Role of Calcium-Activated Potassium Channels in Proliferation, Migration and Invasion of Human Chronic Myeloid Leukemia K562 Cells.

Calcium-activated potassium channels (KCa) are important participants in calcium signaling pathways due to their ability to be activated by an increase in intracellular free calcium concentration. KCa channels are involved in the regulation of cellular processes in both normal and pathophysiological conditions, including oncotransformation. Previously, using patch-clamp, we registered the KCa currents in the plasma membrane of human chronic myeloid leukemia K562 cells, whose activity was controlled by local Ca2+ entry via mechanosensitive calcium-permeable channels. Here, we performed the molecular and functional identification of KCa channels and have uncovered their role in the proliferation, migration and invasion of K562 cells. Using a combined approach, we identified the functional activity of SK2, SK3 and IK channels in the plasma membrane of the cells. Selective SK and IK channel inhibitors, apamin and TRAM-34, respectively, reduced the proliferative, migratory and invasive capabilities of human myeloid leukemia cells. At the same time, the viability of K562 cells was not affected by KCa channel inhibitors. Ca2+ imaging showed that both SK and IK channel inhibitors affect Ca2+ entry and this could underlie the observed suppression of pathophysiological reactions of K562 cells. Our data imply that SK/IK channel inhibitors could be used to slow down the proliferation and spreading of chronic myeloid leukemia K562 cells that express functionally active KCa channels in the plasma membrane.

New characteristics in ECG induced by ultra-high altitude hypoxia

The partial pressure of oxygen decreases significantly with altitude elevation. Adaptive pathophysiological reactions and non-special electrocardiogram(ECG) changes are common in healthy individuals who are exposed to high altitude environments (greater than2500 m). However, previous literatures reported did not fully reflect the characteristics of the plateau ECG changes. A 27-year-old man living for more than 400 days at an ultra-high altitude (5400 m) presented with a rare but urgent ECG features including a right deviation of the electrical axis, pathological Q-wave, a poor increase of R-wave, and T-wave bidirectional/inversion. The erythrocytosis, pulmonary artery pressure, right heart overload and the reversible dynamic evolution of ECGs were gradually improved after he was rapidly transferred to the a low-altitude hospital. This study may provide a new feature of high-altitude induced ECG changes, indicate the potential mechanismand therapeutic value.

Features of hemostasis in patients after severe Covid-19 at discharge from the hospital (original study)

Since 2020, the world has been living in the COVID-19 pandemic caused by the SARS-CoV-2 virus. This situation is due to the high virulence and prevalence of the virus, which has reached epidemic proportions in recent years. Hemostasis disorders are the main marker and prognosis of the severe course of the disease. The virus in the body of a patient with COVID-19 triggers a pathophysiological chain reaction, which, in turn, will lead to the development of a cytokine storm, a disorder in the hemostasis system, and the development of multiple organ disorders. The purpose of the study: to determine and study the influence of various factors on the characteristics of hemostasis in patients with moderate and severe COVID-19. The object of the study were patients with moderate and severe forms of the disease. The following methods were used in the study: standard laboratory diagnostics and hair mineralogram. Results. Moderate and severe courses have clear laboratory markers, with a high probability of developing thrombotic complications, especially in conditions of deficiency of such minerals as zinc, selenium, iron, copper, bismuth, and aluminum, which have immunoregulatory, antioxidant, antiviral, and hemostatic properties, as well as reduce the risk of secondary infection. Conclusions. The results of the study suggest the importance of using minerals and emphasize the significance of using minerals in patients at the very beginning of the disease in order to strengthen the main physiological systems in case of laboratory-confirmed deficiency.

Influence of Semax on the Level of Pro- and Anti-Inflammatory Cytokines in Conditions of "Social" Stress

Introduction: This study was devoted to the experimental study of the effect of Semax (Met-Glu-His-Phe-Pro-Gly-Pro) on the level of pro- and anti-inflammatory cytokines (IL-1β, IL-4, IL-6, TNF-α, TGF-β1) in conditions of "social" stress Aim of the study: to study the effect of Semax on the level of pro- and anti-inflammatory cytokines (IL-1β, IL-4, IL-6, TNF-α, TGF-β1) under conditions of “social” stress. Materials and methods: White nonlinear rats (males, 6–8 months of age) were used as experimental animals. The animals were divided into groups: 1 – the control group (n=10); 2 – animals exposed to "social" stress (20 days) (n=10 aggressors/10 victims); 3 – rats exposed to "social" stress and receiving Semax intraperitoneally at a dose of 100 μg / kg / day (20 days) (n=10 aggressors/10 victims). Sensory contact was chosen as an experimental model of "social" stress. The level of cytokines (IL-1β, IL-4, IL-6, TNF-α, TGF-β1) was determined by the method of enzyme-linked immunosorbent assay. Results: Currently, within the framework of the development of a direction to study the functioning of the unified cytokine network of the body, there is a need for a detailed analysis of changes in the production of individual cytokines during various pathophysiological reactions, including stressful effects. The experimental "social" stress is accompanied by an increase in the production of IL-1β, IL-6, TNF-α, TGF-β1, which allowed us to consider stress as the main inducer of the production of cytokines of the family of proinflammatory interleukins and various growth factors. It was previously thought that inflammation and the immune response are the only factors capable of causing the production of most cytokines. In recent years, scientific works have appeared in which stress occupies an important place among the inducers of cytokine production. This fact has been confirmed by our experiments. Experimental "social" stress is accompanied by changes in the production of IL-1β, IL-4, IL-6, TNF-α, TGF-β1, which allowed us to consider stress as the main inducer of the production of proinflammatory cytokines and growth factors. Conclusion: Evaluation of the effect of Semax on the level of cytokines under conditions of "social" stress showed that the effect of Semax is aimed at restoring the level of the studied cytokines in the group of stressed animals.

Ca2+-regulated enzymes calpain and calcineurin in neurodegenerative processes and prospects for neuroprotective pharmacotherapy

Calcium (Ca2+) and Ca2+-regulated enzymes calpain and calcineurin are the key molecules of signaling mechanisms in neurons and ensure the normal course of intracellular neurochemical and neurophysiological processes. The imbalance and increase in the intracellular level of Ca2+ correlates with the activation of calpain and calcineurin. Inactivation of endogenous inhibitors and/or absence of exogenous pharmacological inhibitors of these enzymes may induce a cascade of intracellular mechanisms that are detrimental to the structural integrity and functional activity of neurons. The interrelated processes of Ca2+ imbalance, dysregulation of calpain and calcineurin are directly related to the development of intracellular pathophysiological reactions leading to the degeneration and death of selective neuronal populations in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. The review briefly presents the characteristics of calpain and calcineurin, their interrelated role in the neurodegeneration processes. Data on the efficiency of the exogenous inhibitors (in vivo, in vitro) point out the potential role of pharmacological regulation of calpain and calcineurin for neuroprotection.

Chronicles of A.I. Pospelov Moscow Dermatovenerology and Cosmetology Society (MDCS was founded on October 4, 1891) Bulletin of the MSDC № 1140

On November 17, 2020, the 1140th meeting was held in on-line format.&#x0D; In total there were 92 participants. Five people were accepted as members of the MDCS.&#x0D; The clinical agenda of the meeting considered cases of subacute (disseminated) cutaneous lupus erythematosus and reactions to tattooing in the form of pseudolymphoma of the skin. The interest of observing disseminated lupus erythematosus was in the difficulties of diagnosis due to its combination with Sjogrens syndrome, a long history of the disease, the severity of the skin process and the peculiarities of the selection of adequate drug therapy. Analysis of the case of pseudolymphoma development as a reaction to a tattoo in a patient with atopic dermatitis helped to approach a more accurate understanding of the clinical and pathogenetic aspects of this process: probably, the pathophysiological reaction is based on a reaction to a foreign body, which makes this disease related to sarcoidosis.&#x0D; The scientific agenda of the meeting reported on the advantages of using photodynamic therapy for skin T-cell lymphomas, such as good cosmetic results; non-invasive nature of the procedure; selectivity; low risk of toxicity; low photosensitivity; low carcinogenic potential. In another report ― on the use of signaling pathway blockers in the treatment of psoriasis ― the results of an open uncontrolled prospective clinical study of the effectiveness of apremilast in the treatment of moderate and severe psoriasis were presented.

The Role of the Human Microbiome in the Pathogenesis of Pain.

Understanding of the gut microbiome's role in human physiology developed rapidly in recent years. Moreover, any alteration of this microenvironment could lead to a pathophysiological reaction of numerous organs. It results from the bidirectional communication of the gastrointestinal tract with the central nervous system, called the gut-brain axis. The signals in the gut-brain axis are mediated by immunological, hormonal, and neural pathways. However, it is also influenced by microorganisms in the gut. The disturbances in the gut-brain axis are associated with gastrointestinal syndromes, but recently their role in the development of different types of pain was reported. The gut microbiome could be the factor in the central sensitization of chronic pain by regulating microglia, astrocytes, and immune cells. Dysbiosis could lead to incorrect immune responses, resulting in the development of inflammatory pain such as endometriosis. Furthermore, chronic visceral pain, associated with functional gastrointestinal disorders, could result from a disruption in the gut microenvironment. Any alteration in the gut-brain axis could also trigger migraine attacks by affecting cytokine expression. Understanding the gut microbiome's role in pain pathophysiology leads to the development of analgetic therapies targeting microorganisms. Probiotics, FODMAP diet, and fecal microbiota transplantation are reported to be beneficial in treating visceral pain.

НЕЙРОГЕННОЕ ВОСПАЛЕНИЕ И ОСОБЕННОСТИ ВЕГЕТАТИВНОЙ НЕРВНОЙ СИСТЕМЫ У ПАЦИЕНТОВ С БРОНХИАЛЬНОЙ АСТМОЙ В ЗАВИСИМОСТИ ОТ СТЕПЕНИ ТЯЖЕСТИ И ФЕНОТИПА ЗАБОЛЕВАНИЯ

Abstract. Bronchial asthma (BA) is a heterogeneous disease characterized by chronic airway inflammation. The central link in the pathogenesis of the disease is the inflammatory process of the bronchial wall, the maintenance of which, along with allergens, infections and toxic agents, is facilitated by "neurogenic" inflammatory factors, and imbalance in the links of the autonomic nervous system. Vasointestinal peptide is involved in bronchodilation and substance P is currently considered as the main mediator of neurogenic inflammation, capable of causing such pathophysiological reactions as pain, mucosal edema, mucus hypersecretion, and bronchoconstriction. The research available to date does not fully reflect the mechanisms and degree of influence of the imbalance of the autonomic nervous system and neurogenic inflammation in patients with severe bronchial asthma. In this regard, the study of autonomic dysfunction and it’s connection with the clinical features of severe bronchial asthma is relevant and can contribute to the improvement of a personalized approach to the treatment of patients with asthma, which is of practical interest. Our study presents the results of the level of neuropeptides depending on the type of dysfunction of the autonomic nervous system, as well as the phenotype of bronchial asthma.