Cut from the same cloth: RNAs transcribed from regulatory elements.

A certain degree of chromatin openness is necessary for the activity of transcription-regulating regions within the genome, facilitating accessibility to RNA polymerases and subsequent synthesis of regulatory element RNAs (regRNAs) from these regions. The rapidly increasing number of studies underscores the significance of regRNAs across diverse cellular processes and diseases, challenging the paradigm that these transcripts are non-functional transcriptional noise. This review explores the multifaceted roles of regRNAs in human cells, encompassing rather well-studied entities such as promoter RNAs and enhancer RNAs (eRNAs), while also providing insights into overshadowed silencer RNAs and insulator RNAs. Furthermore, we assess notable examples of shorter regRNAs, like miRNAs, snRNAs, and snoRNAs, playing important roles. Expanding our discourse, we deliberate on the potential usage of regRNAs as biomarkers and novel targets for cancer and other human diseases.

[A comparative assessment of microbiocenosis of saliva and oropharynx in patients with migraine]. / Sravnitel'naya otsenka mikrobiotsenoza slyuny i rotoglotki u patsientov s migren'yu.

OBJECTIVE: To identify changes in the microbiome of saliva and to compare it with the microbiome of the oropharynx of patients with migraine. MATERIAL AND METHODS: Sixty patients with migraine (21-56 years old), were examined using a headache diary, MIDAS and VAS. A microbiological examination of saliva and smear from the mucosa of the posterior wall of the oropharynx with evaluation by the method of mass spectrometry of microbial markers (MSMM) with the determination of 57 microorganisms was performed. All patients had comorbid chronic diseases of the gastrointestinal tract and upper respiratory tract (URT), according to anamnestic data and examination by specialists. RESULTS: A significant increase in the content of markers of resident (conditionally pathogenic) microorganisms characteristic of chronic diseases of URT (strepto- and staphylococci); markers of transient microorganisms characteristic of intestinal microflora (clostridia, gram-negative rods, anaerobes) that are normally absent; viral markers of cytomegaloviruses and herpes groups; a decrease in the content of fungi were identified in saliva. A comparative analysis of the microbiome of saliva and oropharynx showed: 1) a significant decrease in the concentration of coccal flora Enterococcus spp., Streptococcus mutans, Staphylococcus aureus, anaerobic bacteria Clostridium difficile and Clostridium perfringens in saliva; enterobacteria Helicobacter pylori; gram-negative rods Kingella spp., fungi and Epstein-Barr virus; 2) an increase in salivary concentrations of Staphylococcus epidermidis, anaerobic Clostridium ramosum and Fusobacterium spp./Haemophilus spp. and gram-negative bacilli Porphyromonas spp. CONCLUSION: A comparative assessment of the microbiota of a smear from the posterior wall of the oropharynx and saliva using MMSM showed the presence of dysbiosis both in the oropharynx and in the saliva of patients with migraine. However, there were fewer deviations from the norm in saliva, therefore, for diagnostic purposes, a smear from the posterior wall of the oropharynx is more significant as a biomarker for patients with migraine.

[The role of food allergy as a provoking factor of migraine]. / Rol' pishchevoi allergii kak provotsiruyushchego faktora migreni.

OBJECTIVE: To assess the effect of food allergies on the course of migraine. MATERIAL AND METHODS: Seventy patients with migraine, aged 21-56 years old, were examined using headache diary, MIDAS and VAS, studies of specific antibodies of the IgG4 class (delayed type food allergy) by immuno-enzyme analysis (ELISA), microbiological examination of a smear from the mucous membrane of the posterior wall of the oropharynx with mass spectrometry of microbial markers (MSMM) with the identification of 57 microorganisms. RESULTS: We found an increase in specific IgG4 for a number of food allergens in most patients with migraine, of which 48.5% had a pronounced increase in IgG4 (>150 kEd/l) for at least one allergen (cow's milk - 13% patients, wheat flour - 5%, egg white - 47% or yolk - 26%, quail egg - 15%, sweet pepper - 6%), in 29% of people to several food allergens at once (all of them had chicken egg protein as one of the allergens). There was the association of IgG4 titers to wheat allergen with the severity of headache according to VAS (r-S=0.7; p=0.0046) in patients with the most severe, chronic migraine (17 people) and with an imbalance of the oropharyngeal microbiota, namely, concentration of pathological viruses Herpes spp. (rs=0.29; p=0.02), Epstein-Barr (rs=0.46; p=0.0002) and microscopic fungi (rs=0.39; p=0.0016), detected in these patients. CONCLUSION: We show for the first time the relationship between delayed-type food allergy and redistribution in the microbiome of the oropharynx of patients with migraine and once again confirm the role of delayed-type food allergy as a clinically significant factor influencing the course of migraine (its intensity and chronicity).

[The state of the oropharyngeal microbiome in patients with migraine]. / Sostoyanie mikrobioma rotoglotki u patsientov s migren'yu.

OBJECTIVE: To determine a role of changes in the oropharyngeal microbiome in the development and clinical manifestations of migraine. MATERIAL AND METHODS: Seventy patients with migraine, aged 21-56 years, and 15 healthy subjects matched for age and sex were examined using headache diary, MIDAS and VAS, the Gastrointestinal Symptom Rating Scale (GSRS), microbiological smear examination from the mucous membrane of the posterior wall of the oropharynx with evaluation by the method of mass spectrometry of microbial markers (MSMM) with determination of 57 microorganisms. RESULTS: The following changes in the oropharynx of individuals with migraine compared with the group of healthy individuals (control group) were found: a) a significant increase in the content of markers of resident (conditionally pathogenic) microorganisms characteristic of chronic diseases of the upper respiratory tract (strepto- and staphylococci); b) the appearance of markers of transient microorganisms normally absent, characteristic of the intestinal microflora (clostridia, gram-negative rods, enterobacteria, anaerobes); c) the appearance of viral markers of cytomegaloviruses, Herpes group, Epstein-Barr; d) a significant decrease in the content of bifidobacteria and lactobacilli). All people with migraine had a history or were found on examination to have chronic diseases of the upper respiratory tract (sinusitis in 48%, pharyngitis in 43%, tonsillitis in 25% of people), and gastrointestinal diseases. Dyspepsia was the most frequent and pronounced of the gastrointestinal syndromes on the GSRS in people with migraine (87%). This corresponds to the data on the extremely frequent occurrence of IBS (70% of patients) and other gastrointestinal pathology obtained from the patient history. CONCLUSION: In our work, the microbiota of the oropharynx in patients with migraine was studied for the first time using a new MSMM method. Disturbance of the oropharyngeal microbiome compared to the norm was detected in 100% of people with migraine. The changes characteristic of most patients included a significant decrease in the content of normal flora, an increase in the concentration of conditionally pathogenic microorganisms and the appearance of pathogenic microflora characteristic of chronic diseases of the upper respiratory tract and gastrointestinal tract, which may indicate their role in the pathogenesis of migraine.

[Diagnostic value of chromato-mass-spectrometry in patients with drug-induced jaws osteonecrosis]. / Kliniko-diagnosticheskoe znachenie khromato-mass-spektrometrii pri medikamentoznom osteonekroze cheliustei.

In patients with drag-induced jaw osteonecrosis which developed in cancer patients due to administration of bisphosphonates for metastases, the microflora of the oral cavity was examined by chromatography-mass spectrometry (HMS). The method of HMS can be used as an additional method of diagnostics in complex clinical cases with ineffective treatment.

[The use of immunomodulator likopid in the combined treatment pulmonary tuberculosis]. / Primenenie immunomoduliatora likopida v kompleksnom lechenii tuberkuleza legkikh.

Licopid is a synthetic analogue of a cell wall component of all bacteria. The monocytic macrophageal system is the main target of licopid's action. Addition of the immunomodulator to combined therapy for patients with pulmonary tuberculosis in order to enhance phagocytic activity exerted a marked clinical effect appeared as ceased bacterial isolation in 80% of the patients, a fall in the amount of purulent sputum, no symptoms of intoxication following 2-3 weeks, accelerated resolution of infiltrative changes. The positive clinical effect coincided with the immunological one manifested as increases in the absolute counts of CD3+CD4+ and CD3+CD8+ cells, in the absorptive and bactericidal functions of phagocytes. Such effects were not observed in patients receiving routine treatment. Licopid is recommended for supplementation to the combined treatment regimen for pulmonary tuberculosis.

[Immune status of patients with chronic tonsillitis before and after tonsillectomy]. / Immunnyi status bol'nykh khronicheskim tonzillitom do i posle tonzilléktomii.

Immune status was examined before and after tonsillectomy in 35 patients with various forms of chronic tonsillitis (CT). Measurements were made of main lymphocyte populations, IgA, IgG, IgM levels, functional activity of neutrophils, titers of antibodies to opportunistic microorganisms of the upper airways. It is shown that tonsillectomy produces positive changes in some immunological indices: serum IgG normalized, titers of antibodies to Haemophillus influenzae, Streptococcus pneumoniae and streptolysin-0 lowered, initially low count of B-lymphocytes, natural killers, T-helpers rose, neutrophil chemiluminescence normalized.

[Clinico-immunological effectiveness of likopid in conservative treatment of patients with chronic tonsillitis and chronic sinusitis]. / Kliniko-immunologicheskaia éffektivnost' likopida pri konservativnom lechenii bol'nykh khronicheskim tonszillitom i khronicheskim sinusitom.

30 patients with chronic tonsillitis (CT) and 20 patients with chronic sinusitis (CS) received likopid (4 mg/day for 10 days). CT patients were additionally treated with tonsil lacunar lavage with dioxidine solution. Likopid was found effective in CT patients (good response--31%, partial response--59%). 9% did not respond to likopid. CS patients benefited less (good response--10%, partial response--50%). 40% were non-responders. In CT patients likopid demonstrated also an immunomodulating effect. Positive changes were observed in the counts of B-lymphocytes, T-lymphocytes, T-helpers, natural killers, level of serum IgG, titers of specific antibodies, functional activity of neutrophils. In CS this effect was less pronounced.

[Features of humoral antibacterial immunity in patients with HIV infections and AIDS]. / Nekotorye osobennosti gumoral'nogo antibakterial'nogo immuniteta u BICh-infitsirovannykh i bol'nykh SPIDom.

The level of antibodies to some bacterial antigens, their affinity and relationship to the level of CD4+ T-lymphocytes in persons at different stages of HIV infection was studied. The study revealed that at early stages of the development of HIV infection a decrease in the levels of antibodies to Streptococcus pneumoniae protein somatic antigen in comparison with those in HIV-negative donors occurred. In the process of the development of HIV infection an increase in the level of Staphylococcus aureus peptidoglycan and some S.aureus antigenic determinants, as well as to S.pneumoniae protein somatic antigen, took place. Patients with HIV infection who had non-specific pulmonary diseases exhibited an increased level of antibodies to Branhamella catarrhalis complex ultrasonic antigen. In patients with HIV infection having an amount of CD4+ T-lymphocytes below 200/1 the level of antibodies to bacterial antigen was higher than in patients with an amount of CD4+ T-lymphocytes varying within 200-400/1. In addition, at all stages of HIV infection and in all kinds of its complications an increase in the titer of antibodies to N-acetylglycosoaminylmuramyl dipeptide, an antigenic determinant of peptidoglycan with immunostimulating and adjuvant activity.

[Chronic bacterial prostatitis as a manifestation of secondary immunodeficiency state]. / Khronicheskii bakterial'nyi prostatit kak proiavlenie vtorchnogo immunodefitsitnogo sostoianiia.

The clinico-immunological examination of 57 patients with chronic bacterial prostatitis was carried out. The clinical analysis made it possible to divide the patients into 3 groups characterized by the presence of chronic inflammatory diseases of other organs which had appeared before (group 1) or after (group 2) the manifestation of the symptoms of prostatitis, aw well as by the absence of concomitant inflammatory diseases (group 3). At the same time these patients were found to have changes in their immune status, most pronounced in patients of groups 1 and 2. The clinico-immunological analysis of the patients with chronic bacterial prostatitis revealed the fact that chronic bacterial prostatitis was a chronic inflammatory process linked with changes in the immune system; these changes had the signs of secondary immunodeficiency and required immunocorrective therapy.

[Use of flow cytofluorimetry in the analysis of interactions of mononuclear phagocytes with protein antigens]. / Ispol'zovanie protochnoi tsitofliuorimetrii dlia analiza vzaimodeistviia mononuklearnykh fagotsitov s belkovymi antigenami.

Flow cytofluorometry of samples stained with fluorochrome-labeled antigen may be used to study the interactions between human blood calls and antigens. Using fluorescein isothiocyanate-labeled tuberculin (after the original method), the authors found that human blood monocytes actively bind labeled tuberculin. Studies of the concentrations from 0.1 to 12,500 ng/ml showed that saturation of the cell capacity for endocytosis is attained at certain doses, after which their surface label prevails. The share of tuberculin-binding lymphocytes was appreciably lower than that of monocytes at the same doses of the antigen. Clinical application of the method for assessing the antigen-presenting function of macrophages is discussed.

[The use of immunological indices for assessing the severity of the course of periodontitis and treatment efficacy]. / Ispol'zovanie immunologicheskikh pokazatelei dia otsenki tiazhesti techeniia parodontita i éffektivnosti lecheniia.

The authors studied immunological status of patients with paradontosis. If included estimation of extended structure of lymphocytes and functional status of thymus. There was marked correlation between clinical of patients and immunological indices especially in severe form of paradontitis. As immunological preparation T-activin was used in injections and applications. Using of T-activin gave positive results in patient developed of paradontitis.

[The clinico-immunological evaluation of the ribomunyl treatment of chronic bronchitis patients]. / Kliniko-immunologicheskaia otsenka lecheniia ribomunilom bol'nykh khronicheskim bronkhitom.

The paper reports the results of ribomunil trial in chronic bronchitis (CB) patients who suffered from frequent exacerbations. The drug was found to act primarily on a phagocytic component of the immunity and local immunity of the respiratory mucosa. Because of its vaccine-like effect, ribomunil administration is most beneficial in CB remission. Ribomunil treatment results in reduction of the number and duration of CB exacerbations, of the scope of antibacterial therapy.

Late T cell deficiency in victims of the Chernobyl radiation accident: possible mechanisms of induction.

T cell number, serum concentrations of thymic hormones and anti-epithelial autoantibodies were studied in people affected at Chernobyl NPP. Group 1 took part in the clearing-up operation and had no clinical manifestations of acute radiation sickness. Group 2 worked at the NPP during the accident; they survived acute radiation sickness (degree I-II, subgroup 2a; degree III-IV, subgroup 2b). The total doses of external radiation were 0.1-0.5 Gy in group 1, up to 4 Gy in subgroup 2a and up to 9 Gy in subgroup 2b. Total T cell number, serum thymic activity and alpha 1-thymosin concentration were decreased in all groups of affected persons. CD8+ cell number decreased only in group 1; CD4+ cell number in subgroup 2b. A decrease in thymic hormone level was most prominent in subgroup 2b. The titres of anti-epithelial antibodies were increased in all groups of affected persons independently of radiation dose. The titres were higher in patients with subnormal levels of alpha 1-thymosin. It has been proposed that radiation alters the function of thymic epithelial cells by direct action and/or through indirect mechanisms including participation of autoantibodies. The observed complex of alterations is similar to that in the normal process of immunological ageing.

[Individual immunological parameters in clean-up team members and patients with sequelae of acute radiation sickness 5 years after the effects of the Chernobyl accident]. / Individual'nye immunologicheskie pokazateli u likvidatorov i bol'nykh s posledstviiami ostroi luchevoi bolezni cherez 5 let posle vozdeistviia faktorov Chernobyl'skoi avarii.

A study was made of deviations, beyond 1 sigma and 1.5 sigma of a mean value (M) of a donor group, in individual immunological parameters (for instance, the number of CD5+, CD2+, CD4+, CD8+, CD25+ and B-cells; alpha 1-thymosin concentration; and autoantibody titers to antigens of epithelial reticulum cell cytoplasm) in patients suffered acute radiation sickness (ARS) and liquidators of Chernobyl NPP accident. The radiation damage to the immune system was reliably detected in the affected subjects examined: they exhibited a decrease in the alpha 1-thymosin level below M = -1.5 sigma and in absolute B cellularity below M = -1 sigma; and increase in the number of CD25+ cells and in the level of serum autoantibodies to antigens of thymus epithelial reticulum cell cytoplasm. When several parameters selected were examined simultaneously the frequency of recording the deviations in merely one of them markedly increased.

[Several indices of the peripheral immune system in clean up team workers and patients who survived acute radiation disease 5 years after effects of the radiation accident factors]. / Nekotorye pokazateli perifericheskogo zvena immunnoi sistemy u likvidatorov i bol'nykh, perenesshikh ostruiu luchevuiu bolezn', cherez 5 let posle vozdeistviia faktorov radiatsionnoi avarii.

A group of liquidators and patients survived acute radiation sickness (ARS) was studied five years after the effect of radiation factors resulted from the Chernobyl A.P.S. disaster. Studied were the number of T-lymphocytes (SD2+, SD3+, SD5+), subpopulations SD16+ and SD25+, the content of SD16+ and SD25+ lymphocytes and B-cells, as well as the levels of serum IgM, A, G; determined was the concentration of serum alpha 1-thymosin. A decrease was noted in the number of T-cells of the examined patients, with respect to all markers studied: the number of SD4+ cells was found decreased in patients with ARS sequelae and normal in liquidators. The decrease in serum alpha 1-thymosin was a function of dose. Dynamics of changes in the T-cells of the examinees may reflect the new trends in the radiation response of T-lymphocytes which were not directly related to initial damages to the latter. The injury to the stroma of the thymus and especially to its epithelial cells may be the basis for later postirradiation damages to the immune system. The decrease in the concentration of alpha 1-thymosin in the blood serum of the examinee is the manifestation of the thymus hypofunction. In liquidators and patients with the ARS sequelae the number of SD25+ cells increased markedly indicating the existence of the source of endogenous cell activation. The content of B-lymphocytes in all studied groups of patients was reduced which may serve as a criterion of chronic stress.

[The possibilities of using immunological indices as criteria for determining the stage of HIV infection and the disease prognosis]. / Vozmozhnosti ispol'zovaniia immunologicheskikh pokazatelei v kachestve kriteriev opredeleniia stadii VICh-infektsii i prognoza zabolevaniia.

The authors studied the immune status of 14 HIV-infected patients, 6 of whom had lymphadenopathy, 4 were diagnosed as having AIDS-related complex and 4, a full-blown AIDS. Analysis of laboratory findings showed that of predictive value are serum levels of immunoglobulin B, a CD4 cell count less than 200, reduced populations of CD20 and CD16 lymphocytes, and a depressed response to pokeweed mitogen. Based on the clinical manifestations and laboratory results, three stages characterizing the immune system in HIV infection have been identified.

[The immunological prognosis of complications in patients undergoing reconstructive operations after the radiation therapy of malignant tumors of the maxillofacial area and neck]. / Immunologicheskoe prognozirovanie oslozhnenii u bol'nykh posle luchevoi terapii zlokachestvennykh opukholei cheliustno-litsevoi oblasti i shei pri provedenii rekonstruktivnykh operatsii.

Immunologic studies were carried out in 55 patients with local malignant processes in the maxillofacial area and neck before and after surgery. The patients were divided into 2 groups: group 1 (N = 20) received no specific therapy before surgery, group 2 (n = 35) were administered radiotherapy in a total focal dose of 56-65 Gy before the operation. The findings evidence that radiotherapy augments B and T system immunodeficiency manifestations after surgical stress. Postoperative complications in the patients administered radiotherapy before surgery are due to not only immunodeficiency, but to the initial presence of an infective agent as well. Immunocorrective therapy before and after surgery may be recommended to patients whose immunity parameters are shifted.

[Clinico-immunologic studies in rhinosinusogenic cerebral arachnoiditis]. / Kliniko-immunologicheskie issledovaniia rinosinusogennykh tserebral'nykh arakhnoiditov.

This is a comparative clinico-immunological investigation of 30 virtually healthy persons and 42 patients with rhinosinusogenic cerebral arachnoiditis. In patients considerable changes were detected in immune indices, both cellular and humoral, with a secondary immune deficiency and autoimmune disorders. The group at high risk of immune deficiency was singled out. In each patient the quantifying of the abnormal immune indices can provide additional criterion to evaluation of prognosis of the disease and efficiency of treatment.