Humoral Mechanisms Research Articles

Features of changes in nonspecific factors of immunological reactivity in obesity

Introduction. The study of pathogenetic factors of obesity is an urgent task of modern medicine. The formation of obesity is characterized by changes in the activity of individual mechanisms of innate immunity. At the same time, the values of laboratory indicators that characterize them are often within the current boundaries of the reference values of laboratory indicators of the immunity of a healthy person. This complicates the pathogenetic assessment of the mechanisms of nonspecific immunological reactivity in obesity and determines the need for further study of the characteristics of nonspecific immune defense factors in this pathology.Aim. To identify the features of changes in cellular and humoral factors of nonspecific immunological reactivity in obesity.Materials and methods. A single-center cross-sectional, one-time controlled study was conducted with the participation of 118 people, of which 87 people were obese patients (BMI 37.2 [34.1; 42.05] kg/m2), 31 people had normal body weight (BMI 21.9 [ 20.2; 23.5] kg/m2) and were included in the control group. All patients underwent a study of lipid profile (total cholesterol, high-density lipoproteins, low-density lipoproteins, very low-density lipoproteins, triglycerides), carbohydrate metabolism (glucose, insulin, glycated hemoglobin), C-reactive protein, indicators of cellular and humoral factors of nonspecific immunity (leukogram, cytokine profile, C3-C4 complement components).Results. An increase in the total number of leukocytes was revealed, due to neutrophil granulocytes against the background of the development of a disproportion between the percentage and absolute value of the number of lymphocytes and monocytes, the concentration of C3 and C4 complement components, C-reactive protein, as well as an increase in the level of IL-6, which confirms the presence of low-grade chronic inflammation in obese patients. Statistically significant correlations of immunological parameters with anthropometric data, indicators of carbohydrate and lipid metabolism were revealed.Conclusion. The results of the study indicate that obesity causes activation of certain cellular and humoral mechanisms of nonspecific immune defense involved in the formation of the inflammatory process. Confirmation of the presence of a latent inflammatory process in obesity is an increase in the level of leukocytes and their individual cellular forms, C-reactive protein, C3 and C4 complement components, IL-6. A feature of the changes is the presence of fluctuations in the values of the studied indicators within the current boundaries of the reference values of laboratory indicators, which makes it difficult to timely diagnose chronic inflammation in obesity

Predictive immunoinformatics reveal promising safety and anti-onchocerciasis protective immune response profiles to vaccine candidates (Ov-RAL-2 and Ov-103) in anticipation of phase I clinical trials.

Onchocerciasis (river blindness) is a debilitating tropical disease that causes significant eye and skin damage, afflicting millions worldwide. As global efforts shift from disease management to elimination, vaccines have become crucial supplementary tools. The Onchocerciasis Vaccine for Africa (TOVA) Initiative was established in 2015, to advance at least one vaccine candidate initially targeting onchocerciasis in infants and children below 5 years of age, through Phase I human trials by 2025. Notably, Ov-RAL-2 and Ov-103 antigens have shown great promise during pre-clinical development, however, the overall success rate of vaccine candidates during clinical development remains relatively low due to certain adverse effects and immunogenic limitations. This study, thus, aimed at predicting the safety and immunogenicity of Ov-RAL-2 and Ov-103 potential onchocerciasis vaccine candidates prior to clinical trials. Advanced molecular simulation models and analytical immunoinformatics algorithms were applied to predict potential adverse side effects and efficacy of these antigens in humans. The analyses revealed that both Ov-RAL-2 and Ov-103 demonstrate favourable safety profiles as toxicogenic and allergenic epitopes were found to be absent within each antigen. Also, both antigens were predicted to harbour substantial numbers of a wide range of distinct epitopes (antibodies, cytokines, and T- Cell epitopes) associated with protective immunity against onchocerciasis. In agreement, virtual vaccination simulation forecasted heightened, but sustained levels of primary and secondary protective immune responses to both vaccine candidates over time. Ov-103 was predicted to be non-camouflageable, as it lacked epitopes identical to protein sequences in the human proteome. Indeed, both antigens were able to bind with high affinity and activate the innate immune TLR4 receptor, implying efficient immune recognition. These findings suggest that Ov-RAL-2 and Ov-103 can induce sufficient protective responses through diverse humoral and cellular mechanisms. Overall, our study provides additional layer of evidence for advancing the clinical development of both vaccine candidates against onchocerciasis.

ANCA-Negative Pauci-Immune Glomerulonephritis: A Review

Background: Pauci-immune glomerulonephritis (PIGN) is typically secondary to antineutrophil cytoplasmic antibodies (ANCA) small-vessel vasculitis. However, some cases lack detectable circulating ANCA and are called ANCA-negative PIGN (seronegative PIGN). The reported incidence of this varies greatly. Its relationship to ANCA-associated vasculitis (AAV) is unclear. Summary: This review explores the pathophysiology of seronegative PIGN and summarizes findings from 12 studies focusing on this disease. The role of neutrophils appears to be central, with activation through cellular and humoral mechanisms. Most studies have noted less extrarenal involvement and more chronic changes in the kidney biopsy in seronegative PIGN compared to ANCA-positive cases. Studies have mostly reported using corticosteroids with cyclophosphamide for induction therapy and azathioprine for maintenance. The renal survival was noted to be lower compared to ANCA-positive PIGN. Key Messages: Whether ANCA-negative PIGN represents a distinct disease or is part of the AAV spectrum remains unclear. Prospective large-scale studies are needed to understand this disease for optimal diagnosis and management.

Cytokine landscape in hospitalized children with multisystem inflammatory syndrome

The etiology of multisystem inflammatory syndrome in children (MIS-C), frequently observed following COVID-19 infection, remains elusive. This study unveils insights derived from cytokine analysis in the sera of MIS-C patients, both before and after the administration of intravenous immunoglobulin (IVIG) and glucocorticosteroids (GCS). In this study, we employed a comprehensive 45-cytokine profile encompassing a spectrum of widely recognized proinflammatory and antiinflammatory cytokines, as well as growth factors, along with other soluble mediators. The analysis delineates three principal cytokine-concentration patterns evident in the patients’ sera. Pattern no.1 predominantly features proinflammatory cytokines (IL-6, IL-15, IL-1ra, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor α (TNFα), C-X-C motif chemokine ligand 10 (CXCL10/ IP-10), and IL-10) exhibiting elevated concentrations upon admission, swiftly normalizing post-hospital treatment. Pattern no. 2 includes cytokines (IL-17 A, IL-33, IFNγ, vascular endothelial growth factor (VEGF), and programmed death ligand (PD-L1)) with moderately elevated levels at admission, persisting over 7–10 days of hospitalization despite the treatment. Pattern no. 3 comprises cytokines which concentrations escalated after 7–10 days of hospitalization and therapy, including IL-1α, IL-1β, IL-2, IL-13, platelet-derived growth factor AA/BB (PDGF AA/BB). The observed in cytokine profile of MIS-C patients showed a transition from acute inflammation to sustaining inflammation which turned into induction of humoral memory mechanisms and various defense mechanisms, contributing to recovery.

A recent ongoing effect: Hyponatremia in neurologically ill patients

Different variables altering the volume of extracellular fluid might result in hyponatremia, which is defined as a serum sodium content below 136 millimoles per liter. Depending on the volume status, it can be classified as hypovolemic, euvolemic, or hypervolemic. Hyponatremia is caused by a number of risk factors and drugs, such as diuretics, NSAIDs, and antidepressants. Hyponatremia is more common in patients with neurological conditions, especially those with head trauma, subarachnoid hemorrhage, or acute meningitis. Recent advancements in analysis for disorder of antidiuretic hormone syndrome (SIADH), a prevalent cause, include vasopressin-2 receptor antagonists. The intricate regulation of sodium and water balance by humoral, neurological, and renal mechanisms is a part of normal physiology. Hyponatremia may result from medications such as tramadol, sacubitril/valsartan, antidepressants, and anticonvulsants interfering with these mechanisms. Drug-induced hyponatremia is managed by stopping the offending agent, limiting fluid intake, and occasionally administering hypertonic saline. For chronic hyponatremia, the use of vaptans, like tolvaptan, in conjunction with urea therapy is growing. A risky complication of hyponatremia is osmotic demyelination syndrome, which can occur when the condition is treated too quickly. To avoid negative consequences, close observation and the right amount of fluids must be administered during treatment. To summarize, treating hyponatremia effectively entails determining the underlying causes, treating them, and making sure that serum sodium levels are carefully corrected to avoid consequences such as osmotic demyelination syndrome.

The role of genetic and epigenetic factors on the development of cognitive deficits in patients with severe trauma after repeated anesthesia (literature review)

Introduction. When a severe combined injury occurs in a patient, various biochemical, humoral, cellular and pathophysiological mechanisms of protection against death occur. Immediately after receiving an injury, the patient is hospitalized in a hospital for medical care, where every effort is made to stabilize the condition, resorting to the appointment of various instrumental and laboratory tests. The development and course of traumatic illness, and treatment outcomes in patients with similar injuries are sometimes dramatically different. Based on this, it was suggested that there is a genetic basis for the regularity of the disease, as well as that exogenous factors themselves can affect certain molecular genetic markers, primarily telomere length.The objective was to summarize the current literature data on the study of changes in telomere length, as well as the influence of exogenous and endogenous factors on their shortening. To determine the prospects of studying the effect of polymorphic alleles of various genes on the development of a pathological condition in a certain cohort, namely the development of cognitive dysfunction in patients with severe trauma after repeated anesthesia.Materials and methods. The literature search and analysis was performed in the medical information systems PubMed and eLibrary, using the keywords «telomere», «trauma», «cognitive», and «anesthesia».Results. Since 1950, data on the study of human telomeres began to be published abroad. Between 2002 and the present, 39 articles were published on PubMed when searching for the keywords «anesthesia» and «telomeres»; by keywords «cognitive», «trauma», «telomeres» – 27. Most articles are devoted to the effect of childhood trauma on changes in telomere length, as well as the assessment of short telomeres in patients with various cognitive deficits. However, there are no articles devoted to studying the effect of repeated anesthesia, as an exogenous factor, on the genetic apparatus of a patient with severe combined trauma.Conclusion. The literature highlights the influence of various exogenous factors on the shortening of telomere length, especially in the context of childhood trauma, cognitive impairment in various observed groups. The section related to the effects of anesthesia and their number, the consequences for the genetic apparatus of a particular person, is open for study.

A Systemic Review of the Brain Mechanism of Humor Processing

As a universal linguistic phenomenon, humor has gradually become an interdisciplinary research topic. Domestic and international scholars have expanded the study of humor, yet there is a paucity of evaluations on the brain mechanisms underlying humor perception. This paper primarily introduces the concept of humor, the major theoretical frameworks of humor, and the key findings from domestic and international research on the neural mechanisms of humor. Furthermore, this paper synthesizes the existing issues in humor research in order to provide clues and guidance for future investigations of humor.

Exploring neuronal mechanisms of osteosarcopenia in older adults.

Until recently, research on the pathogenesis and treatment of osteoporosis and sarcopenia has primarily focused on local and systemic humoral mechanisms, often overlooking neuronal mechanisms. However, there is a growing body of literature on the neuronal regulation of bone and skeletal muscle structure and function, which may provide insights into the pathogenesis of osteosarcopenia. This review aims to integrate these neuronal regulatory mechanisms to form a comprehensive understanding and inspire future research that could uncover novel strategies for preventing and treating osteosarcopenia. Specifically, the review explores the functional adaptation of weight-bearing bone to mechanical loading throughout evolutionary development, from Wolff's law and Frost's mechanostat theory to the mosaic hypothesis, which emphasizes neuronal regulation. The recently introduced bone osteoregulation reflex points to the importance of the osteocytic mechanoreceptive network as a receptor in this neuronal regulation mechanism. Finally, the review focuses on the bone myoregulation reflex, which is known as a mechanism by which bone loading regulates muscle functions neuronally. Considering the ageing-related regressive changes in the nerve fibres that provide both structural and functional regulation in bone and skeletal muscle tissue and the bone and muscle tissues they innervate, it is suggested that neuronal mechanisms might play a central role in explaining osteosarcopenia in older adults.

Chlorantraniliprole Enhances Cellular Immunity in Larvae of Spodoptera frugiperda (Smith) (Lepidoptera: Noctuidae).

The innate immunity of insects encompasses cellular and humoral defense mechanisms and constitutes the primary defense against invading microbial pathogens. Cellular immunity (phagocytosis, nodulation, and encapsulation) is primarily mediated by hemocytes. Plasmatocytes and granulocytes play an important role and require changes in the cytoskeletons of hemocytes. However, research investigating the immunological impacts of insecticides on the fall armyworm (FAW), Spodoptera frugiperda, remains scarce. Therefore, we conducted a study to investigate the effects of chlorantraniliprole exposure on cellular immunity in FAW larvae. Our findings revealed the presence of five types of hemocytes in the larvae: prohemocytes, plasmatocytes, granulocytes, oenocytoids, and spherulocytes. The LD10, LD20, and LD30 of chlorantraniliprole affected both the morphology and total count of some hemocytes in the larvae. Moreover, larvae exposed to chlorantraniliprole showed increased phagocytosis, nodulation, and encapsulation. To determine the mechanism of the enhanced cellular immunity, we studied plasmatocytes in the spread state and the cytoskeleton in hemocytes. It was found that the spreading ratio of plasmatocytes and the areas of the cytoskeletons in hemocytes were increased after chlorantraniliprole treatment. These results suggest that exposure to chlorantraniliprole results in an enhanced immune response function in FAW larvae, which may be mediated by cytoskeletal changes and plasmatocyte spreading. Consequently, this study provides valuable insights into the cellular immune response of FAW larvae to insecticide exposure.

EXPERIMENTAL RESEARCH OF THE PHARMACOLOGICAL EFFECT OF CARBON DIOXIDE IN THE CORRECTION OF INFLAMMATION

Osteoarthritis is considered one of the leading causes of chronic disability and is a significant problem on human health and the economy. Chronic pain is the dominant symptom that prompts patients to seek medical attention. Pain mechanisms in osteoarthritis remained unknown for a long time. However, it is known that chronic inflammation of the joint can be a key factor in the occurrence and exacerbation of pain or changes in the perception of pain. Pharmacological therapy is often based on the use of steroidal and non-steroidal anti-inflammatory drugs, but their long-term use or large doses can cause side effects. That is why the development of new methods of treatment of inflammatory processes is the object of active research, as they can affect various mechanisms. In this context, carboxytherapy is an interesting alternative or addition to existing treatment regimens aimed at reducing pain in patients with osteoarthritis. This method involves the administration of medical carbon dioxide (CO2) to improve blood supply to tissues, which can contribute to humoral, biochemical and tissue mechanisms. Studying the effects of carboxytherapy in animal models of inflammation is important for understanding its potential benefits and mechanisms of action. Objective. Study of anti-inflammatory properties of carboxytherapy both in monotherapy and in its combined use. Methods. Carboxytherapy is the injection of carbon dioxide in monotherapy and when used in combination on the formalin model of inflammation in animals. Results. The obtained research results prove the anti-inflammatory properties of carbon dioxide on the model of formalin inflammationin animals. Conclusions. The combined use of carboxytherapy enhanced the effect of conventional drugs on the formalin model of inflammation in animals. The establishment of an anti-inflammatory effect of carboxytherapy indicates the therapeutic value of CO2, while emphasizing the need for further in-depth studies to explore its mechanisms and confirm the efficacy for clinical use.

Gene Expression Level and Immunohistochemical Localization of Cannabinoid and Cannabinoid-Related Receptors in The Small Intestine of Holstein Bulls (Bos Taurus Taurus)

Abstract The gastrointestinal tract plays a crucial role in nutrient absorption, secretion, and motility, ensuring proper digestion and overall homeostasis. Regulation of this complex system involves the coordination of various communication pathways, including neural and humoral mechanisms. One such mechanism is the endocannabinoid system (ECS), a signaling network comprising endogenous cannabinoids, receptors, and enzymes involved in the regulation of physiological processes in mammals and non-mammalian species. While extensive research has been conducted on the ECS in monogastric animals, limited information is available on its presence and distribution in cattle. This study aimed to investigate the distribution and localization patterns of cannabinoid receptors type 1 (CB1R) and type 2 (CB2R) and transient receptor potential vanilloid type 1 (TRPV1) in the bovine small intestine. The study included immunohistochemical analysis of intestinal tissue samples from Polish Holstein-Friesian breed bulls. Gene expression levels of CNR1, CNR2, and TRPV1 genes, encoding CB1R, CB2R, and TRPV1, respectively, were quantified using qPCR analysis. The results showed that all three receptors were expressed in the bovine small intestine, with TRPV1 exhibiting a significant upregulation in the jejunum compared to the duodenum and ileum. Immunoreactivity for CB1R and CB2R was predominantly observed in neurons of the enteric plexuses, while TRPV1 immunolabeling was detected in both enteric neurons and duodenal Brunner’s glands. These findings may establish an anatomical foundation for further investigations, lending support to the potential therapeutic efficacy of cannabinoid receptor agonists in alleviating gastrointestinal motility disorders associated with bovine enteropathies and optimizing milk production in dairy cattle.

Rho kinase inhibitor Y-27632 downregulates IL-1β expression in mice with experimental autoimmune myocarditis

Autoimmune myocarditis is the limited or diffuse inflammation of the myocardium due to dysfunctional cellular and humoral immunity mechanisms. We constructed mouse models of experimental autoimmune myocarditis (EAM) using peptide MyHC-α614-629. On the day after secondary immunization, the mice were intraperitoneally injected with Rho kinase (ROCK) inhibitor Y-27632. On day 21, the cardiac tissues were harvested and weighed. The hearts of EAM mice were significantly enlarged and whitened. Furthermore, body weight (BW) slowly increased during the treatment period, the heart weight (HW) and the ratio of HW/eventual BW were increased, and inflammatory infiltration and fibrosis were aggravated in the myocardial tissue. Y-27632 treatment improved the aforementioned phenotypic and pathological features of EAM mice. Mechanistic analysis revealed a significant increase in Notch1, Hes1, Jag2, Dil1, Toll-like receptor (Tlr) 2, and interleukin (IL)-1β expression in the myocardial tissue of EAM mice. Notably, IL-1β expression was correlated with that of Notch1 and Tlr2. Following Y-27632 treatment, the expression of key target genes of the Notch signaling pathway (Notch1, Hes1, Dil1, and Jag2) and Tlr2 were obviously decreased. Y-27632 treatment also decreased the number of monocytes in the spleen of EAM mice. Thus, ROCK inhibitor Y-27632 exerted a protective effect in EAM mice by downregulating IL-1β expression. This study aimed to provide a reference point for the future treatment of myocarditis in clinical settings.

A tetravalent dengue virus-like particle vaccine induces high levels of neutralizing antibodies and reduces dengue replication in non-human primates.

Dengue virus (DENV) represents a significant global health burden, with 50% of the world's population at risk of infection, and there is an urgent need for next-generation vaccines. Virus-like particle (VLP)-based vaccines, which mimic the antigenic structure of the virus but lack the viral genome, are an attractive approach. Here, we describe a dengue VLP (DENVLP) vaccine which generates a neutralizing antibody response against all four DENV serotypes in 100% of immunized non-human primates for up to 1 year. Additionally, DENVLP vaccination produced no ADE response against any of four DENV serotypes in vitro. DENVLP vaccination reduces viral replication in a non-human primate challenge model. We also show that transfer of purified IgG from immunized monkeys into immunodeficient mice protects against subsequent lethal DENV challenge, indicating a humoral mechanism of protection. These results indicate that this DENVLP vaccine is immunogenic and can be considered for clinical evaluation. Immunization of non-human primates with a tetravalent DENVLP vaccine induces high levels of neutralizing antibodies and reduces the severity of infection for all four dengue serotypes.IMPORTANCEDengue is a viral disease that infects nearly 400 million people worldwide and causes dengue hemorrhagic fever, which is responsible for 10,000 deaths each year. Currently, there is no therapeutic drug licensed to treat dengue infection, which makes the development of an effective vaccine essential. Virus-like particles (VLPs) are a safe and highly immunogenic platform that can be used in young children, immunocompromised individuals, as well as healthy adults. In this study, we describe the development of a dengue VLP vaccine and demonstrate that it induces a robust immune response against the dengue virus for over 1 year in monkeys. The immunity induced by this vaccine reduced live dengue infection in both murine and non-human primate models. These results indicate that our dengue VLP vaccine is a promising vaccine candidate.

Potential Aspects of the Use of Cytokines in Atopic Dermatitis.

Atopic dermatitis (AD) is an abnormal inflammatory response in the skin to food, environmental IgE, or non-IgE allergens. This disease belongs to a group of inflammatory diseases that affect both children and adults. In highly developed countries, AD is diagnosed twice as often in children than in adults, which may possibly be connected to increased urbanization. The immune system's pathomechanisms of AD involve humoral mechanisms with IgE, cellular T lymphocytes, dendritic cells occurring in the dermis, Langerhans cells occurring in the epidermis, and other cells infiltrating the site of inflammation (eosinophils, macrophages, mast cells, neutrophils, and basophils). Cytokines are small proteins that affect the interaction and communication between cells. This review characterizes cytokines and potential aspects of the treatment of atopic dermatitis, as well as new strategies that are currently being developed, including targeting cytokines and their receptors.

When should chatbots express humor? Exploring different influence mechanisms of humor on service satisfaction

As artificial intelligence technologies evolve, a discernible trend is emerging wherein chatbots are imbued with the capability to articulate emotions within online customer service. However, the research on emotional expression by chatbots is still in its infancy, and the existing research on this aspect is inconclusive. Therefore, from the perspective of chatbots expressing humor, this study proposes a boundary condition for the effectiveness of chatbot-expressed humor and a different influence mechanism of expressing humor in different dialogues on service satisfaction through four experimental studies. Our study found that chatbots' expression of humor in chit-chat dialogues leads to higher perceived entertainment and service satisfaction for customers; however, chatbots' expression of humor in task-oriented dialogues leads to distraction and lower service satisfaction. In addition, we found that entertainment significantly mediated between humor in chit-chat dialogues and service satisfaction, while distraction had a significant indirect effect between humor in task-oriented dialogues and service satisfaction. These findings deepen our understanding of chatbot-expressed humor and provide valuable insights into online retailers’ deployment of humorous chatbots.

Impact of different types of pain on organizational decisions in palliative medicine

In press This short scientific report reveals important aspects of palliative medicine use of narcotic and non-narcotic analgesics, antidepressants, and anticonvulsants. Specific indications and restrictions on their use, routes of drug administration (oral, intravenous, intramuscular, subcutaneous, transdermal, intrarectal) are defined. The issues of monitoring the dosage of narcotic painkillers by medical personnel and patients themselves, the administration of bolus doses, and the medical equipment necessary for this were discussed. Special attention is paid to such pharmaceuticals as morphine, oxycodone, buprenorphine, butorphanol, morphine. The study of pathogenesis, clinical manifestations, diagnostic methods and the arsenal of therapeutic agents for overcoming acute and chronic pain in palliative patients is important for the organization of hospice and palliative care (HPC). Different types of pain are described depending on the nosological forms, individual sensitivity to pain, sensitization to pain, ways of transmitting the pain signal from the peripheral to the central part of the nervous system, humoral mechanisms of increasing and decreasing the sensation of pain, pain assessment on the Visual Analogue Scale. The need for organizational solutions to improve the situation with analgesia in Ukrainian palliative and hospice institutions, in particular to increase the availability of effective analgesia for palliative patients, was identified. Improving the situation with pain relief corresponds to the national strategy of Ukraine for the development of the HPC system. The report makes a comparison with the development of such a system in Great Britain on the way to one of the best systems of medical care for palliative patients, and on the basis of the futuristic development models described in the literature, it is assumed that Ukraine is on a similar path. Keywords: nociception, somatic pain, visceral pain, neuropathic pain, narcotic analgesics, non-narcotic analgesics.

Characteristics of neurovegetative disorders in ischemic heart disease patients after coronavirus disease 2019 (COVID-19)

The aim of the study. To examine the frequency and spectrum of cognitive, anxiety-depressive, autonomic disorders and their interrelationship in patients with coronary heart disease (CHD) after COVID-19 infection. Materials and methods. The study involved 71 patients with CHD, stable angina pectoris FC II–III (age 69.0 [64.0; 76.0] years): group 1 (main) – 31 CHD patients after COVID-19; group 2 (comparison) – 40 CHD patients without COVID-19 history. Spectral and temporal HRV parameters were assessed using 24-hour Holter ECG monitoring, anxiety-depressive disorders (ADD) – using the HADS scale, cognitive status of patients – according to the MoCa scale. Results. CHD patients after COVID-19 had a higher frequency of ADD detection and a greater anxiety level (16 [10; 24] versus 10 [9; 13] points, p < 0.05), depression (14 [8; 20] versus 11 [10; 12] points, p < 0.05) as compared to patients without previous history of COVID-19. At the same time, the predominance of the anxiety component over the depressive one in patients of both groups has been revealed. In CHD patients after COVID-19, a decrease in the total MoCa scale score has been found as compared to patients without COVID-19: 24 [22; 26] versus 28 [26; 30] points, p < 0.05. There was an association between the total level of anxiety and depression and the severity of cognitive impairment (r = -0.36, p < 0.05). CHD patients exposed to COVID-19 showed an increased sympathetic and parasympathetic tone of the central nervous system within 24 hours, an increased LF/HF ratio during the active period, activation of slow-acting humoral regulation mechanisms amid increasing stress index and centralization index. In the group of patients with CHD after COVID-19, a wide range of correlations between the rate of ADD, cognitive disorders and HRV parameters has been found. Conclusions. Patients with coronary heart disease recovered from COVID-19 have shown an increase in the incidence and degree of ADD and cognitive disorder manifestations which was accompanied by autonomic dysfunction resulting in stress on the functional and adaptive state of the cardiovascular system. The association between ADD, autonomic and cognitive disorders in patients with coronary heart disease after COVID-19 has confirmed the common pathogenetic links of the disorders found.

Abstract 2788: Immunological targeting of integrin β1high/β3high melanoma

Abstract We previously reported two integrin β4 (ITGB4)-targeted immunologic strategies, e.g., ITGB4 protein-pulsed dendritic cells (ITGB4-DC) for vaccination and adoptive transfer of anti-CD3/anti-ITGB4 bispecific antibody (ITGB4 BiAb)-armed tumor draining lymph node (TDLN) T cells. Both immunotherapies significantly demonstrated efficacy in inhibiting local tumor growth and lung metastases. We found these therapeutic efficacies were closely associated with the T cell as well as humoral anti-integrin β4high cancer stem cells (CSCs) in breast (4T1) and head and neck squamous cell carcinoma (SCC7) tumor models. Recently, we further found that integrin subunits β1 (ITGB1) and β3 (ITGB3) are expressed at significantly high level in melanoma cells. In culture cell lines, integrin β1 and β3 are highly expressed on approximately 98% and 95% of the two mouse melanoma cell lines F10 and D5. We confirmed the expression of these two integrin subunits in newly harvested fresh melanoma tumors in vivo, which is very similar to the findings in cell lines. We then assessed ITGB1 and/or ITGB3-pulsed dendritic cell (DC) vaccines using F10 mouse model and demonstrated that ITGB1-DC or ITGB3-DC vaccine both exhibited significant antitumor efficacy inhibiting tumor growth, and ITGB1-DC + ITGB3-DC showed an additive/synergistic anti-tumor effect. Notably, we found that ITGB1 and ITGB3 loaded on separate DCs demonstrated more potent antitumor efficacy than loaded on the same DCs as vaccine. In addition, anti-PD-L1 significantly augmented the antitumor efficacy of ITGB1-DC/ITGB3-DC vaccine to inhibit tumor growth. Considering the crucial role of CSCs in tumor initiation, progression, metastasis, and recurrence, we further evaluated the expression of ITGB1 and ITGB3 on F10 and D5 ALDHhigh CSCs. We detected significantly higher expression of ITGB1 on ALDHhigh F10 CSCs (83.3%) and ALDHhigh D5 CSCs (87.1%) vs. ALDHlow F10 non-CSCs (0.2%) and ALDHlow D5 non-CSCs (2.0%), suggesting that ITGB1 and ITGB3-targeted vaccine-conferred anti-melanoma effects may have significantly involved targeting of ITGB1high/ITGB3high melanoma CSCs. Furthermore, recent studies suggested that bone marrow (BM)-DCs expressing dysfunctional integrin β2 (ITGB2) exhibited more potent antigen presentation function than WT BM-DCs. We found that ITGB2 highly (63.3%) expressed on the surface of BM-DC, but not on F10 or D5 tumor cells. On-going experiments include the investigation of experimental evidence to verify that ITGB1 and ITGB3-targeted vaccines have induced targeting of ITGB1high/ITGB3high melanoma CSCs; and both the cellular and humoral mechanisms underlining the anti- ITGB1high/ITGB3high melanoma CSC immunity. At the same time, generation and use of ITGB2 deficient DCs for the vaccine preparation to improve the efficacy of DC vaccine targeting integrin ITGB1high/ITGB3high melanoma and melanoma CSCs warranty further investigation. Citation Format: Feng Wang, Ying Xin, James J. Moon, Alfred E. Chang, Max Wicha, Qiao Li. Immunological targeting of integrin β1high/β3high melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2788.

Exercise-induced potentiation of the acute hypoxic ventilatory response: Neural mechanisms and implications for cerebral blood flow.

A given dose of hypoxia causes a greater increase in pulmonary ventilation during physical exercise than during rest, representing an exercise-induced potentiation of the acute hypoxic ventilatory response (HVR). This phenomenon occurs independently from hypoxic blood entering the contracting skeletal muscle circulation or metabolic byproducts leaving skeletal muscles, supporting the contention that neural mechanisms per se can mediate the HVR when humoral mechanisms are not at play. However, multiple neural mechanisms might be interacting intricately. First, we discuss the neural mechanisms involved in the ventilatory response to hypoxic exercise and their potential interactions. Current evidence does not support an interaction between the carotid chemoreflex and central command. In contrast, findings from some studies support synergistic interactions between the carotid chemoreflex and the muscle mechano- and metaboreflexes. Second, we propose hypotheses about potential mechanisms underlying neural interactions, including spatial and temporal summation of afferent signals into the medulla, short-term potentiation and sympathetically induced activation of the carotid chemoreceptors. Lastly, we ponder how exercise-induced potentiation of the HVR results in hyperventilation-induced hypocapnia, which influences cerebral blood flow regulation, with multifaceted potential consequences, including deleterious (increased central fatigue and impaired cognitive performance), inert (unchanged exercise) and beneficial effects (protection against excessive cerebral perfusion).

Funny? Think About It! Selective effect of cognitive mechanisms of humour on insight problems

ABSTRACT The present study aims to elucidate whether insight problem solving could be facilitated by the cognitive component of humour. The authors take interest in whether the logical mechanisms of humour can affect how fast insight problems are solved. To that end, the authors conducted two experiments where participants solved insight problems after watching visual humorous stimuli such as videos and slideshows. The first experiment demonstrated the overall impact of facilitation by humour on insight problem solving; however, it did not show any difference in how particular logical mechanisms of humour affect the solution time of insight problems. The second experiment showed that the cognitive component of humour could selectively affect insight problems whose difficulty stems from different sources. These results suggest that the cognitive component of humour, when operationalised as logical mechanisms and schema switching, contributes to solving insight problems.