Phytocompounds and their molecular targets in immunomodulation: a review

Immune cells are important for the healthy function of every organ. The homeostasis of the immune system is selfregulated by T-cells, B-cells, and natural killer cells. The immunomodulation process of immune cells is part of the immunotherapy. According to therapeutic methods of immune responses are categorized as inducing (immunostimulant), amplification (immune booster), attenuation (immunomodulation), and prevention (immunosuppressive) actions. The prevalence of chronic immunological diseases like viral infections, allergies, and cancer is mainly due to the over-activation of the immune system. Further, immunomodulators are reported to manage the severity of chronic immunological disorders. Moreover, these immunomodulator-acting proteins are identified as potential molecular targets for the regulation of the immune system. Moreover, natural compound like phytocompounds are known to bind these targets and modulates the immune system. The specialized phytocompounds like curcumin, quercetin, stilbenes, flavonoids, and lignans are shown the immunomodulatory actions and ameliorate the immunological disorders. The present scenario of a COVID-19 pandemic situation has taught us the need to focus on strengthening the immune system and the development of the most promising immunotherapeutics. This review is focused on an overview of various phytocompounds and their molecular targets for the management of immunological disorders via immunosuppressants and immunostimulants actions.

Integrative Analysis of Gut Microbiota and Fecal Metabolites in Rats after Prednisone Treatment

Prednisone is widely used in chronic glomerular diseases, immunological disorders, and rheumatic diseases for its anti-inflammatory and immunosuppressive properties. It is a synthetic glucocorticoid (GC) that shows therapeutic effects after conversion to prednisolone by the liver.

LV-GLS is a predictor of all-cause death and cardiovascular MACE events in patients with neuro-immunological disorders

Background Neuro-immunological disorders encompass several disease states, including multiple sclerosis (MS), autoimmune encephalitis (AE) and myasthenia gravis (MG). These autoimmune conditions are mediated via pro-inflammatory cytokines, and there is growing evidence to suggest cardiovascular involvement within these inflammatory states. Left ventricular global longitudinal strain (LV-GLS) is proposed to be a more sensitive measure of LV systolic function when compared to standard two-dimensional measures such as LV ejection fraction (LVEF). Purpose The purpose of this study was to assess for subclinical cardiac dysfunction in a cohort of patients with neuro-immunological disorders and correlate this with the development of outcomes on follow-up. Methods Consecutive patients with MS, AE and MG admitted to our institution during 2013–2020 were assessed (n=102). Patients without pre-existing cardiovascular disease, LVEF <50% or lack of comprehensive transthoracic echocardiography during their index admission were included (n=55). This group was compared to age- and gender-matched controls (n=55) LV-GLS was measured offline using vendor-independent software (TomTec Arena, Germany v4.6) by two cardiologists blinded to the patient group or outcomes. These patients were followed for up for the composite outcome of all-cause death and major adverse cardiovascular events (MACE). Results A total of 55 patients (31 MS, 14 AE and 10 MG) were age- and gender- matched to 55 controls. There was no significant difference in baseline demographic characteristics or cardiovascular risk factors between groups. Patients with neuro-immunological disorders demonstrated impaired LV-GLS (−17.6±3.5 vs −20.8±1.9; p<0.01) when compared to healthy controls, despite an LVEF within the normal range (60.9±7.7 vs 64.1±5.7; p=0.02) in both groups. There were a total of 9 (16.4%) outcomes during a mean follow-up of 41.0±33.0 months. LV-GLS was the only significant echocardiographic predictor of all-cause death and MACE events (p=0.013) on multi-variate analysis. Conclusions Our results suggest that patients with neuro-immunological disorders have subclinical LV dysfunction as assessed by LV-GLS which has prognostic capacity in this population. Further larger studies are required to further characterize this phenomenon. FUNDunding Acknowledgement Type of funding sources: None.

IMMUNOLOGICAL DISORDERS OF THE REPRODUCTIVE SYSTEM THAT OCCUR WHEN EXPOSED TO BENZENE, IN EMPLOYEES OF OIL-PRODUCING ENTERPRISES

Introduction. The protection of the reproductive health of the working-age population is the most important direction of State policy. In 5-15% of cases, the causes of reproductive dysfunction are immunological disorders. Benzene belongs to the group of industrial reprotoxicants, however, its effect of benzene on the reproductive system has not been sufficiently studied. Objective: to study the immunological aspects of the effect of benzene on the reproductive system. Methods. We examined 50 men exposed to benzene with reproductive disorders (26-49 years old), as well as 4 workers with normal sexual function aged 53-60 years. Spontaneous and induced changes in the cellular expression of apoptosis markers were studied. For the study, the ANNEXIN V-FITC/7-AAD kit was used for the detection of cells that have undergone apoptosis. The experiment was conducted in vitro using a biological medium (ejaculate). A factor of the chemical nature was benzene. Results. According to the results of the comparative analysis, there were no significant deviations of pathogenetic tests of immunological markers in comparison with the reference level in the spontaneous expression samples, but there was an excess of expression of the CD95 + cell death receptor (p<0.05) in 30% of the samples examined, and a decrease in the number of Annexin V-FITC+7AAD negative cells (without reaching the significance level) in samples with a load of (15%). There was a difference in the expression levels of CD95+ and CD25+ CD-reception indicators by 20% and 10% in relation to the spontaneous level (p<0.05). Representatives of the chemical group of aromatic hydrocarbons realize reprotoxicity, using the mechanism of excessive induction of the membrane signaling of the cell death receptor, accelerate the natural program of cell death by approximately 20% compared to the state of reproductive cells that were not stimulated. Conclusion. At the present stage, one of the tasks of occupational medicine is to study the effect of chemicals on the processes of reproduction, to develop new approaches to assessing the risk of their impact on the reproductive health of workers.

COVID-19 Vaccination in Fragile Patients: Current Evidence and an Harmonized Transdisease Trial

Patients diagnosed with malignancy, neurological and immunological disorders, i.e., fragile patients, have been excluded from COVID-19 vaccine trials. However, this population may present immune response abnormalities, and relative reduced vaccine responsiveness. Here we review the limited current evidence on the immune responses to vaccination of patients with different underlying diseases. To address open questions we present the VAX4FRAIL study aimed at assessing immune responses to vaccination in a large transdisease cohort of patients with cancer, neurological and rheumatological diseases.

POS0520 ASSOCIATIONS BETWEEN THE NEOVASCULARIZATION OF CAROTID ATHEROSCLEROTIC PLAQUES, LIPID PARAMETERS AND IMMUNOLOGICAL DISORDERS IN PATIENTS WITH RHEUMATOID ARTHRITIS

Background:Development of carotid atherosclerotic plaques (CAP) in patients (pts) with rheumatoid arthritis (RA) is associated with accumulation of traditional risk factors and immunological disorders. CAP neovascularization is associated with its’ inflammation and increasing vulnerability. Therefore, early detection of CAP neovascularization is important for prevention of potential cardiovascular complications, preferably using a non-invasive technique, such as contrast-enhanced ultrasound (CEUS) of the carotid arteries.Objectives:to identify the relationship between the severity of CAP neovascularization, lipid parameters and RA-related parameters.Methods:Evaluation of 23 RA pts, 8 males and 15 females, mean age 61 [58; 65] years, with a longstanding disease (7 [3;12] years), seropositivity for IgM rheumatoid factor (RF) (76%) and anti-cyclic citrullinated peptide (ACCP) (62%) and moderate clinical disease activity (DAS 28 3,9 [3,2;4,8]). Nineteen RA pts (83%) received Methotrexate, 35% - biological agents, 35% - low-dose glucocorticoids. All patients underwent bilateral CEUS of the carotid arteries using a PHILIPS IU22 ultrasound system with 3-9 MHz linear array transducer and i/v administration of SonoVue contrast agent. The severity of carotid intraplaque neovascularization (IPN) was visually assessed on a scale from 0 to 3 (Shah et al. 2007): 0 - no neovascularization, 1 (mild) - limited to moderate neovascularization, 2 (severe) - extensive appearance of neovascularization, 3 - in the presence of a pulsating vessel in the plaque image.Results:Carotid IPN was found in all RA pts. Grade 1 of neovascularization was established in 39% pts (group I) and Grade 2 - in 61% pts (group II). Groups were comparable in terms of age, sex, body mass index, smoking, disease duration and activity RA (DAS 28 score). The degree of carotid IPN positively correlated with the LDL-C level (R = 0,46, p=0,04), and the TG level (R=0,56, p=0,01) and negatively correlated with the HDL-C level (R= -0,52, p=0,02) in all pts. The degree of neovascularization was also associated with RA duration (R=0,52, p<0,05) and ACCP-positivity (R=0,57, p=0,007). Aforementioned correlations were significant for both groups of RA pts. No association was found between the severity of IPN and the levels of RF, DAS28. Association between the degree of carotid stenosis and CRP concentrations (R=-0,73, p<0,05) was found in pts of group II.Conclusion:CEUS of carotid arteries demonstrated the presence of a predominantly extensive carotid IPN in RA pts. Cases of more severe carotid IPN were associated with lipid parameters (positively with the LDL-C, TG levels and negatively with the HDL-C level), RA duration and ACCP-positivity. The relationship between the degree of carotid artery stenosis and CRP requires additional studies to determine the role of immunological disorders in the development of carotid intraplaque neovascularization in RA pts.References:[1]Shah F., Balan P., Weinberg M., Reddy V., Neems R., Feinstein M., Dainauskas J., Meyer P., Goldin M., Feinstein S.B. Contrast-enhanced ultrasound imaging of atherosclerotic carotid plaque neovascularization: a new surrogate marker of atherosclerosis? Vasc Med. 2007;12(4):291-7. https://doi.org/10.1177/1358863x07083363Disclosure of Interests:None declared