Phagocytic activity (PA) of blood leukocytes for Yersinia pestis reflects the state of cellular anti-plague immunity in humans and laboratory animals. The purpose of this work was to evaluate the stimulatory effect of anti-plague vaccination on the PA of peripheral blood leukocytes by in vitro assay using flow cytometry and a biofluorescent strain of Y. pestis EV NIIEG pTurboGFP-B (KM2115), expressing the green fluorescent protein (GFP). We studied leukocytes the 100-μL samples of heparinized whole blood of mice, guinea pigs and humans that were vaccinated with live plague vaccine, as compared with non-vaccinated controls. The suspensions of living KM2115 cells were mixed to blood samples diluted with physiological solution. The result of the phagocytic reaction was assessed after 15 minutes by flow cytometry thus determining the proportion of active phagocytes in the granulocyte gate that showed intense fluorescence in the green area of the spectrum. The data analysis was carried out by the previously developed protocol based on experiments with killed plague microbes labeled with FITC dye. The obtained experimental data have suggested an opportunity of using a biofluorescent Y. pestis strain for the rapid determination of granulocyte PA by flow cytometry in microvolumes of whole blood from humans and animals without longer preliminary staining of microbes with a fluorescent dye. Increased values of phagocytic indices were registered for blood cells of people and animals vaccinated against plague, thus being consistent with data on the stimulatory effect of anti-plague vaccination on the phagocytic function of leukocytes. The use of a biofluorescent strain has simplified the procedure for modeling the interaction of macroorganism cells with plague microbes and subsequent assessment of neutrophil PA in whole peripheral blood, thus enabling its usage to characterize the magnitude of post-vaccination anti-plague immune response by an in vitro test.
The search for probiotic strains with anti-inflammatory properties is an urgent problem in modern microbiology, immunology and biotechnology. Probiotic therapy is a new concept in dentistry. Probiotic drugs are available as a variety of commercial forms, including tablets, toothpaste, mouth rinses. Probiotics affect immune function by regulating local and systemic mechanisms, interacting with epithelial cells of the oral cavity, thereby enhancing the barrier function of the mucous membrane, both in healthy people and in patients with various dental disorders. The aim of this study was to evaluate the effect of the probiotic rinse aid “ImmunitDominos” upon secretion of pro- and anti-inflammatory cytokines, immunoglobulins and lysozyme in oral fluid of healthy people. The material for the study included 64 oral fluid samples obtained from conditionally healthy people aged 30 to 76 years divided into 2 groups during the study: 1, with initially low cytokine values in the oral fluid; and 2, without somatic diseases, but with high cytokine values. The ingredient composition of the mouthwash “ImmunitDominos” was represented by a dry concentrate of five probiotic strains of bifidobacteria (the content of bifidobacteria in one sachet package is at least 108 CFU/g). The mouthwash “ImmunitDominos” was used twice a day for 28 days. The levels of IgA, IgM, IgG (AO Vector-Best, Russia) and cytokines IFNγ, TNFα, IL-17, IL-6, IL-10, IL-1ra (Cytokine LLC, Russia) were determined in oral fluid samples of the subjects examined by the ELISA method; Lysozyme was assayed by a turbidimetric method. The use of a probiotic rinse aid in the subjects of group 1 did not affect the level of cytokines, but led to an increase in lysozyme contents. It was found that the subjects of the 2 group showed a decreased level of IgG and proinflammatory cytokines, especially IL-17, IL-6, TNFα, as well as an increase in the anti-inflammatory IL-1ra. The results obtained revealed the anti-inflammatory effect of the probiotic mouthwash “ImmunitDominos”, thus allowing to recommend it as a potentially preventive agent that increases the local protection of the oral cavity.
Among bacterial infections that threat female health and life, urinary tract infections take a leading position among reasons for hospitalization and the development of negative reactions during pregnancy. The fundamental importance for the onset and end of acute pyelonephritis is given to the state of the innate link of immunity. A special role in the formation of the “cytokine cascade” belongs to various types of cytokines. An increased incidence of pyelonephritis in pregnant women shows insufficient awareness, as well as a lack of understanding various aspects of the pathogenesis in this disease, especially regarding cytokine status of pregnant women at the local and systemic levels. The aim of our work was to study the dynamics of cytokine profile in peripheral blood plasma in acute pyelonephritis at different trimesters of pregnancy before and after treatment. The study included 143 women (mean age 25.3±5.2 years), divided into different groups. I.e., comparison group included healthy non-pregnant women and women with physiological pregnancy in the 1st, 2nd, and 3rd trimesters without kidney pathology; main group consisted of pregnant women with acute serous pyelonephritis in the 1st , 2nd and 3rd trimesters of pregnancy, as well as two groups of women with acute pyelonephritis in the 2nd and 3rd trimesters of gestation with basic treatment including the immunomodulator Viferon, or without this medication. The dynamics of changes in the cytokine profile before and after treatment were studied in the samples of peripheral blood plasma. In acute serous pyelonephritis, the cytokine content at the systemic level was increased, in the course of pregnancy, especially, over 2nd and 3rd trimesters, thus suggesting the presence of immune inflammation. The basic treatment does not fully normalize the altered parameters of cytokine profile, mainly in the 2nd and 3rd trimesters of gestation. The best corrective effect is achieved by pharmacotherapy with the addition of Viferon to the basic treatment. The results of this work expand the existing views on the participation of cytokines in pathogenesis of acute pyelonephritis during different trimesters of pregnancy.
Psoriasis is a chronic systemic inflammatory disease primarily affecting the skin, characterized by excessive keratinocyte proliferation and T lymphocyte infiltration. This multifactorial condition results from complex interactions between genetic, environmental, and immune factors. This retrospective study analysed the demographic, clinical, and therapeutic profiles of 136 psoriasis patients admitted to the Internal Medicine and Dermatology departments of the University Hospital Centre of Sidi Bel Abbès (Western Algeria). The cohort showed a balanced sex distribution (50.7% male, 49.3% female) with a mean age of 51.28±14.19 years. The most prevalent forms were erythrodermic (45.8%), vulgaris (32.2%), and pustular (19.2%). The main treatments included corticosteroids (45.6%), topical creams and emollients (27.2%), and immunosuppressants (25%). Laboratory findings revealed elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), reflecting chronic systemic inflammation. Patients with high ESR levels also exhibited increased blood glucose, blood pressure, triglycerides, and total cholesterol. These findings reinforce the systemic nature of psoriasis and highlight the importance of investigating its molecular and immunological mechanisms. They also support the need for comprehensive and personalized management, especially in the context of associated comorbidities such as cardiovascular disease.
Putrescine and cadaverine are biogenic polyamines that result from the breakdown of the amino acids ornithine and lysine, respectively, and, as a rule, under participation of bacteria. It was revealed that putrescine and cadaverine are able to influence functional activity of innate immune cells at the sites of inflammation. The potential of these compounds to interact with immune cells by changing their activity, including synthetic abilities, causes interest in studying the production of immunoglobulins (Ig) by plasma cells in the presence of polyamines, especially, within inflamed area. The aim of research was to evaluate the effect of cadaverine and putrescine on the production of IgG in cultured mononuclear leukocytes of patients suffering with maxillofacial phlegmon. Leukocytes were obtained from 13 patients with maxillofacial phlegmon and 10 healthy donors. After washing the cells, they were brought to the wells, where B cell mitogen (PWM) and polyamines were added at concentrations of 5, 25, 50, 75 and 100 mmol/L. An equal volume of nutrient medium was added to the control wells instead of polyamines. At the end of cultivation, a supernatant was collected, where the concentrations of immunoglobulins G (IgG) were determined using the enzyme immunoassay method. In the absence of polyamines, higher IgG production by mononuclear cells of patients with acute purulent process (27.6±2.2 IU per 1 g of protein) was revealed compared with healthy donors (13.6±1.5 IU per 1 g of protein; p = 0.002) showing a positive correlation. When culturing patients’ lymphocytes in the presence of polyamines, we have found that cadaverine at all concentrations did not significantly change IgG production in mononuclear culture. When using putrescine, it was found that this metabolite in the culture of mononuclears in dose-dependent manner reduces their IgG production. Putrescine and cadaverine have a multidirectional effect on IgG production in the culture of mononuclear leukocytes of patients with facial phlegmon, due to their role in inflammatory events.
Hashimoto’s thyroiditis (HT) is a common autoimmune thyroid disorder characterized by the gradual destruction of the thyroid gland. It is influenced by a complex interplay of genetic, environmental, and lifestyle factors. Among these, environmental triggers such as smoking, dietary patterns, psychosocial stress, and vitamin D3 deficiency are increasingly recognized for their potential to modulate thyroid autoimmunity. Iraq, with its unique environmental and dietary conditions, presents a valuable context to investigate these associations. Objective: to evaluate the relationship between key environmental factors – specifically smoking, dietary habits (iodine and gluten intake), psychosocial stress, and vitamin D3 levels – and the profiles of thyroid autoantibodies in Iraqi patients diagnosed with HT. This cross-sectional study enrolled 96 Iraqi patients (38 males, 58 females) diagnosed with HT from December 2023 to December 2024 in Baghdad. Data on lifestyle and dietary habits were collected through structured interviews. Laboratory assessments included measurements of thyroid hormones (T3, T4, TSH) and autoantibodies (anti-thyroglobulin [anti-TG], anti-thyroid peroxidase [anti-TPO], and TSH receptor antibody [TRAb]) using ECLIA and CMIA analyzers. Statistical analyses included chi-square tests and logistic regression models to identify associations. Female patients demonstrated a higher prevalence of anti-TPO positivity (75%) than males (55%). Smoking, more frequent among males, was significantly associated with lower TRAb levels. While all participants consumed iodine-rich diets, 85% also followed gluten-rich diets. Vitamin D3 deficiency was observed in over 40% of participants, though it was not significantly associated with autoantibody levels. Gluten intake showed a mild association with T4 levels. Psychosocial stress had no significant impact on thyroid biomarkers. Notably, anti-TPO levels showed a positive correlation with patient age. Environmental factors, particularly smoking and dietary habits, appear to influence thyroid autoimmunity in Iraqi HT patients. Public health interventions focusing on smoking cessation and dietary management may contribute to better disease control. Further prospective studies are needed to confirm these findings.
Variability of human immune deficiency virus (HIV), as well as individual characteristics of the subjects is the reason for the failure of immune system against HIV infection. An imbalance in cytokine production occurs in HIV infection, thus leading to deterioration of immune response. Due to a variety of properties, certain cytokines may protect against HIV infection, while others contribute to the development of immunodeficiency state. At the same time, the immunodeficiency virus can promote the synthesis and production of cytokines. Our study was conducted at the Republican AIDS Center of the Republic of Uzbekistan and Institute of Immunology and Genomics (Academy of Sciences of the Republic of Uzbekistan). The diagnosis in all patients under study was confirmed clinically and by laboratory tests using ELISA and immunoblotting techniques. The HIV-infected participants were aged 9-18 years. The HIV-infected children were divided in two age groups: Group I (9-14 years old), and Group II (15-18 years old). Evaluation of IL- 4, IL-18, TNFα and IFNγ cytokines was performed in HIV-infected children aged 9-18 years. The revealed imbalance of cytokines contributed to the damage of CD4+ cells by the virus, leading to the progression of immunosuppression and subsequent development of opportunistic infections. The significantly increased levels of IL-18, TNFα, and IFNγ were found in HIV-infected children. IL-18 and TNFα have proven to be increased in the older age group, along with decreased IFNγ levels. Elevated levels of IL-18 and TNFα may suggest an active immune response to HIV. Development of chronic inflammatory processes presumes a progression of the disease and emergence of concomitant diseases. Changes in the cytokine synthesis cause dysregulation of immune response in HIV-infected children, which, in turn, may lead to increased viral replication. An increase in IL-4, IL-18, TNFα levels in adolescents, and a decrease in IFNγ during antiretroviral therapy (ART) suggests a need for studying the possible causes of these changes for each child individually, and further adjustment of treatment for HIV-infected children.
Over last decade, microbial biosurfactants, being conventionally used as emulsifiers and solubilizers of hydrophobic substances, have attracted attention as potential biomedical agents, due to their unique biological effetcs that are not found in synthetic analogs, i.e., their antibacterial, antifungal, antiviral, antitumor, or immunomodulatory activity depending on the molecular structure. The purpose of the work was to study the effect of Rhodococcus biosurfactant and its monoacyltrehalose fraction on the production of IL-2, IL-4, IFNγ, IL-17, apoptosis of CD4+ and CD8+ splenocytes caused by a single oral administration, as well as upon humoral and cell-mediated immunity as well as on host versus graft (HVG) response during a course of in vivo oral administration. We have found that a single oral administration of monoacyltrehalose fraction of Rhodococcus biosurfactant caused inhibition of ConA-induced production of IL-2 and IFNγ, stimulated IL-4 production and had no effect on IL-17 levels in splenocytes. Unfractionated Rhodococcus biosurfactant had an inhibitory effect only on IFNγ production. Oral administration of monoacyltrehalose to mice resulted in decreased percentage of early and late apoptosis of CD8+ lymphocytes, and lower rates of late apoptosis of CD4+T cells. Only the percentage of early apoptosis among CD8+T cells was reduced by unfractionated biosurfactant. During 24 hours in ConA-stimulated cultures from mice treated with monoacyltrehalose, we have found a significantly reduced percentage of CD4+ cells in late apoptosis. When being orally administered, the monocyaltrehalose fraction led to a decreased number of nucleated cells in the spleen, inhibition of antibody levels, as well as milder severity of DTH and HVG responses. Thus, oral administration of the monoacyltrehalose fraction of Rhodococcus biosurfactant to mice resulted in decreased Th1 cytokine production, which contributes to a shift in Th0 differentiation towards Th2 cells. The monoacyltrehalose fraction had no apoptogenic effect and, on the contrary, reduced the percentage of late apoptosis of CD4+ and CD8+T lymphocytes. Therefore, apoptosis of lymphoid cells is not a potential mechanism of immunosuppression induced by the components of Rhodococcus ruber biosurfactant.
Tetraspanins (TSPANs) are a family of transmembrane proteins implicated in diverse cellular processes, including signal transduction and cell adhesion. While their precise functions are still being elucidated, their involvement in cancer, particularly leukemia, is increasingly recognized. This study focuses on the multifaceted roles of two specific TSPANs, CD9 and CD81, in acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL), with a specific emphasis on their impact on chemotherapy response. Previous research has established CD9 as a prognostic marker in B cell ALL (B-ALL), with expression correlating with specific genetic subtypes and glucocorticoid resistance. However, its role in other leukemia subtypes and its precise contribution to chemoresistance remain incompletely understood. Similarly, CD81 has been shown to mediate chemoresistance in B-ALL by facilitating protective interactions with the bone marrow microenvironment, but its significance in CLL and its broader impact on chemotherapy sensitivity require further investigation. This study addresses these gaps by investigating the expression of CD9 and CD81 in ALL and CLL patients, stratified by chemotherapy regimen, including vincristine (VCR), methotrexate (MTX), and doxorubicin (DOXO). Our results demonstrate a statistically significant upregulation of both CD9 and CD81 at the gene and protein levels in ALL patients treated with chemotherapy compared to controls. Furthermore, we observed significant upregulation of CD9 in untreated CLL patients, while no significant difference in CD9 or CD81 expression was found between the ALL and CLL groups. These findings strongly suggest a critical role for CD9 and CD81 in mediating chemoresistance in ALL, particularly in the context of VCR, MTX, and DOXO treatment. Based on these observations, we discuss potential mechanisms by which CD9 and CD81 contribute to leukemogenesis and propose that targeting these TSPANs may represent a novel therapeutic strategy to overcome chemoresistance and improve patient outcomes in leukemia.
Liver is a compartment of the immune system, containing the cells of innate and adaptive immunity (populations of CD4+ and CD8+T cells, B lymphocytes). Dysregulation of immunity leads to pathological inflammation, characterized by progressive organ damage. The study of functional changes in various body systems, organs and tissues, including those occurring under participation of immune system, is an important area of modern fundamental and applied research in medicine and biology. The aim of our study is to assess the proportion of CD8+, CD4+, CD79a and Fascin+ cells in the liver during physical activity of varying intensity. The experiments were carried out in male rats by reproducing physical activity of varying intensity. Animals of all series underwent 10 sessions of swimming load, followed by withdrawal from the experiment immediately after the last session. The liver of the animals was removed, paraffin blocks were prepared, stained with hematoxylin and eosin, and immunohistochemical studies were performed for CD8+, CD4+, CD79a, and Fascin+ cell populations. The presented study revealed that, after light physical activity, the studied markers did not change compared to the intact group. With moderate physical load, the proportion of CD4+ cells increased by 1.5 times. A reaction from T helpers, which underlies the cell-mediated immune response, was noted. Following a course of severe physical activity, the proportion of CD8+ cells was increased by 2.4 times (p = 0.002); Fascin+, by 3.8 times (p = 0.04), and CD79a+ cells, by 2.5 times (p = 0.002) compared to the intact group. A change of T killer amounts was detected, and the humoral link of the immune system was also involved. Histological examination revealed features of tissue alteration and inflammatory reaction. There was activation of T cell immune response, mainly due to CD8+ lymphocytes. When studying correlation interactions during moderate physical activity, the relationship between CD4+/CD8+ was strong (r = 0.8; p 0.05). A moderate relationship was also determined between CD79a/Fascin (r = 0.7; p 0.05) during moderate and severe physical activity. Upon severe physical activity, strong correlation interactions were detected between CD8+/CD4+ (r = -0.8; p 0.05). A strong positive relationship was found between Fascin/CD79 (r = -0.8; p 0.05). Liver damage during heavy physical loads is associated with reaction of cellular and humoral links of immunity. Histologically, some alteration-like features and inflammatory reaction were noted in the liver tissue.
The aim of this study is to reveal the proposed associations of the serum IgA and IgG antibodies against Bp, E2 and Pg, as well as E2 and Pg, with expression of ER, PR and Ki-67 in tumor during breast cancer progression (BCP). The content of these antibodies and hormones in the blood serum at BCP I stage (n = 721) and II-IV stages (n = 853) was studied using ELISA technique. Tumor ER, PR and Ki-67- positive cells were detected using immunohistochemical methods. The percentage of BCP with high levels of Ki- 67 positive tumor cells ( 20%) at the II-IV stages was higher than at the I stage independently of IgA-Bp, IgA-E2 and IgA-Pg levels, also depending on the individual IgA-E2/IgA-Pg ratios (р 0.001). Such increase of Ki-67 positive tumors was statistically insignificant in BCP with low IgA-Bp/IgA-Pg ratios ( 1, p = 0.07). Decrease of ER+/PR+ and increase of ER-/PR- tumors were insignificant in BCP with average levels of IgA-Bp (2-4 conventional units, CU; р = 0.07) and IgA-Pg (1-2 CU, p = 0.11), low ratios of IgA-Bp/IgA- Pg 1 (p = 0.43), and IgA-E2/IgA-Pg 1 (р = 0.99). In all other cases, the ER+/PR+ transformation was statistically significant (p 0.01). There were no associations of ER, PR and Ki-67 tumor transformation with the IgG antibodies under study. The percentage of BCP with high levels of Ki-67 positive cells in tumor was not increased when E2 serum concentration was low ( 100 pMol/L, p = 0.11), and when Pg/E2 ratio was high ( 6, р = 0.06). Increase of ER-/PR- tumors proportion was insignificant in BCP with low Pg levels ( 400 pMol/L, p = 0.24) and low Pg/E2 ratios 3 (р = 0.13). Immunoassay technique for IgA-Bp, IgA-E2 and IgA-Pg is proposed for assessing tumor progression in BCP, i.e., proliferation rates and transformation of steroid receptors.
In the subjects infected with HIV, the influence of rs8084 polymorphism suggests that certain alleles may prolong the disease progression at an older age, thus allowing people with specific genotypes to maintain higher CD4 levels even if they are infected later in life. This may indicate a more effective activation of the immune response with age. The present study analyzed the distribution of HIV-1 patients by disease stages depending on age groups, as well as changes in CD4+ per cent levels, and the expression of the MX2, IFNM1, and ADAR1 genes in infected patients. A total of 143 patients diagnosed with HIV-1, aged 14 to 66 years, have been examined. The control group consisted of 67 practically healthy individuals aged 15 to 57 years, who were unrelated, had no clinical signs of HIV infection, and had no hereditary predisposition to the disease. The highest number of infections occurs at the third stage of the disease (symptomatic phase) among young individuals aged 14-35 years. At later stages of the disease, CD4% levels are significantly decreased, indicating the progression of immune deficiency. A correlation was also revealed between the HLA-DRA genotype and CD4% levels, highlighting the potential for a personalized approach to HIV treatment. Moreover, the study revealed a significantly increased expression of the MX2, IFNM1, and ADAR1 genes in HIV-infected patients, thus confirming activation of antiviral mechanisms in response to infection. The study demonstrated that HIV- 1 infection is associated with significant changes in the immune system, as evidenced by a decrease in CD4% levels and an increase in the expression of key antiviral genes such as MX2, IFNM1, and ADAR1. Given the role of genetic factors, such as HLA-DRA polymorphism, in disease progression, the importance of a personalized treatment approach is emphasized.
The study of antibodies with catalytic properties, in particular IgG with oxidoreductase activities, is a relatively new direction in cancer pathology, with very few publications. The aim of the present work was to investigate the catalase and superoxide dismutase (SOD) activities of IgG from patients with colorectal cancer (CRC) depending on the clinical and morphologic parameters of the disease. Blood serum samples from 20 patients with colorectal cancer (T3-4N0-2M0) with high- and low-differentiated tumors and 18 conditionally healthy donors was used in the study. The groups were comparable by sex and age. IgG was purified from serum by affine chromatographic method on column with Protein-G-Sepharose using a AKTA pure chromatograph (GE, USA). Dialysis of antibodies was performed against 20 mM phosphate buffer, pH = 7.0. IgG concentration was determined by spectrophotometric method on a Varioskan LUX multifunctional reader (Thermo Scientific, USA). Electrophoretic analysis of the obtained samples was carried out according to the Lemmli method in PAGE gradient (4-18%). Visualization of the gels was performed using an iBright Imaging Systems FL1500 (Thermo Scientific, USA). Catalase and SOD activities of the antibody samples were spectrophotometrically determined on a Varian Cary 60 UV-Vis spectrophotometer (Agilent, USA). Statistical processing of the data was carried out in Statistica 12.0 program. In the present work, we have shown for the first time that IgG’s of CRC patients are able to catalyze catalase and SOD reactions, and that this activity is an intrinsic property of the antibodies. It was revealed that both studied IgG activities were significantly increased in patients compared to healthy individuals. It has been shown that IgG catalase activity in CRC patients at the II stage of malignancy is 1.8 times higher (p = 0.015) than in CRC patients with the III stage of tumor process. The IgG catalase activity in patients with low-differentiated CRC proved to be two-fold lower (p = 0.045) than in patients with highly differentiated CRC. On the contrary, IgG SOD activity in patients with highly differentiated CRC is 1.7 times lower (p = 0.021) in comparison with patients with low-differentiated CRC. Thus, the studied oxidoreductase activities of abzymes in patients with CRC obviously make a significant contribution to the pathogenesis of CRC and may be used for prognosis of the disease development.
Cancer remains one of the leading causes of morbidity and mortality worldwide, despite significant advancements in conventional therapies such as chemotherapy, radiotherapy, and immunotherapy. However, these approaches often come with severe side effects, treatment resistance, and limited efficacy in certain tumor types, underscoring the urgent need for alternative therapeutic strategies. This meta-analysis explores the therapeutic potential and safety profile of bacterial-based cancer therapies through a systematic review of both preclinical and clinical studies. By targeting the unique properties of the tumor microenvironment, specific bacterial species have shown an ability to preferentially colonize cancerous tissues, modulate immune responses, and serve as delivery vehicles for therapeutic agents. In preclinical models, bacterial treatments demonstrated significant tumor growth inhibition and improved survival outcomes, with minimal systemic toxicity. Clinical trials evaluated a range of bacterial species including engineered forms of Salmonella, Listeria, Clostridium, and Bifidobacterium. Findings indicated varied levels of efficacy in terms of tumor response rates, progression-free survival, and overall survival across different patient cohorts. While some bacterial therapies were associated with notable therapeutic benefits, particularly in prolonging survival and enhancing immune activation, others showed limited efficacy or were accompanied by high rates of adverse events, especially in treatments involving Listeria-based agents. Conversely, Bifidobacterium-based therapies appeared to offer a more favorable safety profile. The heterogeneity in outcomes highlights the influence of bacterial strain, tumor type, dosage, and treatment combinations. This analysis concludes that bacterial-based therapies represent a promising frontier in oncology, offering a unique mechanism of action and potential synergy with existing treatments. Nevertheless, further large-scale and controlled clinical studies are necessary to optimize bacterial selection, enhance delivery mechanisms, and mitigate toxicity risks. Advancing this therapeutic modality could significantly contribute to the development of more personalized, targeted and effective cancer treatments in the future.
The article considers different species of Artemisia and their importance in seasonal allergic diseases, especially pollinosis. Artemisia pollen allergens are a major cause of sensitisation in late summer and autumn worldwide, including Europe, Asian-European Silk Road and the Northwest of USA. About 10-14% of allergic individuals worldwide react to wormwood pollen allergen, and about 25% of these patients develop hypersensitivity to certain foods such as celery, honey, sunflower seeds, chamomile and pistachios. The mugwort pollen allergens range from 350 to 500 species worldwide, with 187 species found in China alone. Some of these species, such as Artemisia annua, are invasive species in Europe and the Americas, being potentially serious sources of allergies. The major allergens of Artemisia pollen are v 1 and v 3 species, which are found worldwide. In Mongolia, the pollen load of wormwood pollen allergens was analysed from 1980 to 2000. The Artemisia pollen allergens are important in Mongolia, especially Artemisia siversiana and Artemisia macrocephala species. The wormwood pollen season in Mongolia lasts from mid-July to mid-August. Allergen-specific immunotherapy (ASIT) is a key component of the treatment of wormwood pollen allergy. It effectively relieves symptoms and reduces the risk of asthma and sensitisation to new allergens. ASIT may result in prolonged remission and reduce the need for baseline and symptomatic therapy. Currently, sublingual immunotherapy is preferred over subcutaneous immunotherapy due to its better safety profile and higher compliance. In summary, the article shows the importance of wormwood pollen allergen as a major allergen, and recent advances in specific immunotherapy for the treatment of wormwood sensitisation.
Previously it has been shown that steroid hormones, estradiol and progesterone (E2 и Pg); antibodies of A and G class against benzo[a]pyrene (IgA1-Bp and IgG1-Bp), estradiol (IgA1-E2 and IgG1-E2), progesterone (IgA1-Pg and IgG1-Pg) and corresponding antiidiotypic antibodies (IgG2-E2 and IgG2-Pg) may influence breast carcinogenesis. It was proposed that some of these effects way be enhanced or inhibited upon combined action of these factors in breast cancer (BC) patients. Hence, only some of these hormones and autoantibodies may show significant associations with tumor growth. Our study aimed for searching effects of E2 и Pg, IgA1-Bp and IgG1-Bp, IgA1-E2 and IgG1-E2, IgA1-Pg and IgG1-Pg, IgG2-E2 and IgG2-Pg in regulation of tumor proliferation in BC patients. Blood serum autoantibodies in 1258 BC cases (620 with I stage and 638 with II-IV stages) were studied using ELISA technique. Concentrations of steroid hormones were measured using “ImmunoEA-Estradiol”, and “ImmunoEA-Pg” (JSC “Immunotech”, Russia). Tumor Ki-67 was determined by standard immunohistochemical technique. Statistical analysis of the results was performed using CART algorithm of Statistica13.0 Software. The contents of Ki-67 positive cells in tumors of stage I BC were increased when blood serum Pg concentrations were high and depended on levels of IgA1-Bp, IgG1-Bp, IgA1-E2 and IgG2-E2. The levels of Ki-67 positive cells in tumors of II-IV stages BCP were high when IgG2- Pg were low and IgA1-Bp were increased. The levels of these factors were similar in blood serum of stage I and stage II-IV patients. Hence, the revealed difference in associations of tumor proliferation with studied serum factors could be dependent on changes of tumor cells receptivity during cancer progression. Immunoanalysis of IgG2-Pg and IgA1-Bp may be used for determination of tumor proliferation in BCP. It is proposed to study antiproliferative properties of artificially produced antibodies against Pg receptor for replenishment of IgG2-Pg deficiency in BCP.
The increasing incidence of pelvic inflammatory diseases, latent course of inflammation, difficulties in isolating the infectious agent contribute to the search for new diagnostic markers to confirm the etiologic factor. Objective of our study was to assess the levels of antibodies to herpes simplex virus (HSV) and cytomegalovirus (CMV), and to characterize the vaginal microbiome in women with chronic cervicitis and reproductive disorders. The prospective study included 72 patients aged 18-45 years. A questionnaire, general clinical, gynecological and instrumental examinations were conducted. Bacteriological, PCR, and serological techniques were used. Ethical principles were observed, the study was approved by the local biomedical ethics committee. Statistical processing of the obtained data was performed using the StatSoft Statistica 6.1 application package. In total group, the frequency of class G antibodies to HSV was 79%, and to CMV, 92% (p 0.05). Within the vaginal microbiome, a combination of microaerophiles with Mycoplasma species was most common in 33%; a combination with HPV was noted in 26%; in 19%, its combination with Candida infection was observed. In the group of patients with complaints for pathological leucorrhoea (45%), the frequency of IgG titers 3200 to HSV type 1.2 was 84%, and IgG titers 3200 to CMV were found in 41% of cases (p 0.001). Bacteria of intestinal group were observed in the vaginal microbiome (p 0.001). In asymptomatic chronic cervicitis, IgG titers 3200 to CMV infection were observed in 25%, and IgG titers 3200 to HSV were revealed in 68% of patients (p 0.001). The microbiome is represented by symbiotic microorganisms (p 0.001) and facultative anaerobic Gram-positive microorganisms. High serological prevalence of specific class G antibodies (IgG) to HSV and CMV infection indicates the presence of persistent herpes infection. In the cases of pathological leucorrhoea, the microbiome is enriched by intestinal microorganisms. Asymptomatic course of chronic cervicitis was accompanied by the presence of Candida infection in symbiosis with Ureaplasma and Gardnerella, and facultative anaerobic gram-positive microorganisms.
Neurological disorders, including MS and pediatric neurodegenerative diseases, pose a significant global health burden with limited therapeutic options (HSCT). Autologous HSCT has emerged as a promising intervention to halt disease progression, reduce disability, and modulate immune responses in the central nervous system. This systematic review and meta-analysis evaluate the clinical outcomes and safety of autologous HSCT in patients with neurological disorders. Following PRISMA guidelines, we searched PubMed, Embase, Cochrane Library, and Web of Science for studies on autologous HSCT in neurological disorders. Included studies reported clinical outcomes (e.g., Expanded Disability Status Scale [EDSS] changes, progression-free survival [PFS]) and complications). Data were synthesized using random-effects meta-analyses to calculate standardized mean differences (SMD) for EDSS changes, pooled proportions for PFS and relapse-free survival, and treatment-related mortality (TRM) rates. Heterogeneity was assessed with I2 statistics, and predictors of outcomes were explored via meta-regression and subgroup analyses. Fifteen studies (n = 1,378 patients) were included, predominantly focusing on MS (relapsing-remitting, progressive, and aggressive subtypes). Autologous HSCT significantly reduced disability, with a pooled SMD in EDSS of -1.02 (95% CI: -1.42, -0.62; p 0.01; I2 = 88.9%). PFS was 73% (95% CI: 0.61-0.84; I2 = 0%), and relapse-free survival in relapsing-remitting MS was 82% (95% CI: 0.70-0.92; I2 = 5%). TRM was low at 2% (95% CI: 0.00-0.04; I2 = 38.9%), with common adverse events including febrile neutropenia and infections. Younger age, shorter disease duration, and relapsing-remitting MS subtype predicted better outcomes (p 0.05). Conditioning regimen influenced safety, with BEAM-based protocols showing lower TRM (p = 0.0049). Autologous HSCT demonstrates significant efficacy in reducing disability and preventing disease progression in neurological disorders, particularly MS, with a favorable safety profile. However, high heterogeneity and limited controlled trials highlight the need for larger, randomized studies to confirm comparative efficacy against standard therapies and optimize patient selection and treatment protocols.
Unhealthy lifestyles such as consuming less nutritious foods, lack of physical activity trigger accelerated aging. Aging occurs due to inflammatory processes in the body associated with increased levels of interleukin-6 (IL-6). IL-6 is a major pro-inflammatory cytokine involved in pathogenesis of various chronic diseases, including cardiovascular disorders, diabetes, and autoimmune conditions. Increased levels of IL-6 are associated with systemic inflammation and poor health outcomes. In recent decades, physical exercise has received attention not only for its role in improving fitness but also as a non-pharmacological intervention to modulate the immune response. Currently, there are scarce data on effects of exercise on the IL-6 response. The underlying mechanisms are also still not clearly understood. The physiological response of exercise to IL-6 is important to know and the underlying molecular mechanisms must be clearly understood in order to understand the stages related to the effect of exercise on increasing IL-6. The objective of this study was to determine the mechanism by which physical activity lowers IL-6 levels. In this systematic review, we searched through literature databases including Science Direct, Web of Science, MEDLINE-Pubmed, and Scopus. Our inclusion criteria covered the papers published over the past five years that addressed IL-6 and physical exercise. The Web of Science, Pubmed, and Science Direct databases were used to locate a total of 126 published papers. For this systematic review, ten papers that met the inclusion criteria were selected and examined. Standard operating procedures were evaluated in this study using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Based on the results of this systematic study, it is evident that chronic exercise reduces IL-6 levels. Immediately after acute physical exercise, IL-6 levels are increased. However, there was a downward trend in IL-6 levels during chronic physical exercise. Chronic and regular exercise has been shown to reduce IL-6 levels. as a marker of inflammation. If IL-6 levels may be suppressed through exercise, inflammation will decrease, thus preventing aging which is triggered by the accumulation of inflammatory factors.
Macrophages are actively involved in recognition, capturing, and destruction of foreign pathogens, as well as removal of cellular debris. The most important role of macrophages is to initiate and regulate the inflammatory response: they synthesize and secrete a wide range of proinflammatory cytokines that activate other immune cells and promote the development of inflammation. The functional state of macrophages directly depends on mitochondrial activities, both as energy suppliers, and as key participants in signaling pathways associated with production of reactive oxygen species and inflammasome activation. Mitochondrial dysfunction may lead to excessive macrophage activation and chronic inflammation, typical of diseases like atherosclerosis and metabolic disorders. Damaged mitochondria release components such as mtDNA and cardiolipin, potentially triggering autoimmune responses. To prevent these events, the cells are capable of mitophagy, a selective autophagy process that removes dysfunctional mitochondria via the lysosomal pathway. Polyunsaturated fatty acids are known to influence inflammation and mitochondrial function, including mitophagy. Arachidonic acid, a precursor of prostaglandins and leukotrienes, modulates immune responses, but its role in mitophagy remains unclear. The aim of this study was to investigate whether arachidonic acid affects mitophagy and the proinflammatory response of human macrophages. Primary monocytes were isolated from whole blood of healthy donors and differentiated into macrophages over 5 days. The cells were treated with 20 μM arachidonic acid for 24 hours, followed by 1 μg/mL LPS stimulation for another 24 hours. Cytokine secretion (TNF, IL-6, IL-8, CCL2) was measured by ELISA technique. Mitophagy was assessed using confocal microscopy by evaluating co-localization of mitochondrial and lysosomal dyes. The results showed that arachidonic acid enhanced mitophagy and reduced secretion of TNF, IL6, and CCL2 in response to LPS. These findings suggest that activation of mitophagy may contribute to the anti-inflammatory effects of arachidonic acid in macrophages.
