Immunological Status Research Articles

The Effect of Acute and Chronic Noise Stress Exposure on some Physiological and Immunological Parameters in Male and Female Adult Mice

Noise, the most commonly encountered stressor in our daily lives, affects the body in different ways depending on its frequency, intensity, and duration. Thus, this study aimed to demonstrate the effect of noise stress exposure in different durations on the immunological status of femaleand maleadult mice. Sixty femaleand male adult mice (Balb/C)were used in this. Fifty mice were exposed to noise stress at 90degreesfor four hours per day,and 10mice (5males and 5females) were left without exposure to stress which was used as a control group. Exposure stress mice were divided into five groups (n =10, 5males and 5females); Group1 was exposed to noise stress for only 1day, Group2 for 8days, Group3 for 14days, Group4 for 21days, and Group5 for 30days. The blood sample was collected and used for immunoglobulins, glucocorticoids and WBCs indices tests. Results showed that there was a highly significant increase in glucocorticoids for all periods after noise exposure. WBCcount, the level of IgG and IgM were highly significantin mice that were exposed to noise stress during1,8,14, and 21 days, while there was no significant difference in the 28-days stress group compared to control. In conclusion, the levels of immunoglobulins levels after 28 day of noise stress exposure could completely differ from the short-term exposure.

Biological subgroups in melanoma: A correlation of tumor genomic and transcriptomic analysis with spatial immunophenotyping.

e14667 Background: A prominent challenge advancing immunotherapy is the heterogeneity of resistance mechanisms leading to drug development failure despite efficacy in subgroup of patients. To address these shortcomings, precision medicine platforms aimed at prospectively stratifying patients into treatment groups based on tumor mutational burden (TMB) and tumor inflammation scores by gene expression profiling (GEP) are now being explored. Whether these gene-based variables reflect the true immunologic state of the tumor remains an open question. Here, we sought to evaluate TMB and GEP as markers of intratumoral inflammatory state by single-cell spatial analysis. Methods: Under an IRB approved protocol through the Huntsman Cancer Institute, 25 melanoma tumors with available clinical, WES, and RNAseq data were stained with a multiplex immunofluorescence-based protocol using Opal dye and Leica Bond Rx (CD8, CD68, PD1, PD-L1, Ki67, SOX10, DAPI) and scanned with Akoya Polaris whole slide scanner. Images were analyzed using HALO. Results: Melanoma tumors were stratified into 4 subgroups based on TMB (<10 vs ≥10 m/Mb) by WES, and inflammatory (Inflm) gene signature expression (GSEA >0 vs ≤0) by RNAseq, denoted as S1 (TMBhi/Inflmhi; n=4), S2 (TMBhi/Inflmlo; n=4), S3 (TMBlo/Inflmhi; n=8), and S4 (TMBlo/Inflmlo; n=9). The rate of disease progression was 0% (S1), 25% (S2), 25% (S3), and 56% (S4). Infiltration analysis of CD8 T cells showed elevated intratumoral CD8 density in S1 (249/mm2) and S3 (157/mm2) vs S2 (65/mm2) and S4 (65/mm2; p=0.0002), consistent with GEP findings. Spatial analysis showed a similar pattern of CD8 distribution across subgroups with peak CD8 density in the tumor periphery. Proximity analyses showed average distance of CD8 T cell to the nearest tumor cell was not different across subgroups. Furthermore, we found Inflmhi tumors had a higher frequency of PD1+ CD8 T cells relative to Inflmlo tumors (12.9 vs 2.8 cells/HPF; p=0.0002), suggesting GEP also reflects CD8 activation and functional status. Increased frequency of PD1+ CD8 T cells was correlated with a much improved overall survival (HR=3.3; p=0.017). A similar analysis performed on CD68+ macrophages showed significantly increased peri-tumoral macrophage recruitment in S4 (445/mm2) vs S1 (209/mm2; p<0.0001), S2 (91/mm2; p<0.0001), and S3 (267/mm2; p=0.0003) subgroups. Interestingly, Inflmhi tumors were associated with an increased proportion of PDL1+ macrophages regardless of TMB status (43% vs 3%; p<0.0001), suggestive of an upregulated adaptive immune response in tumors with active inflammation. Conclusions: Our findings illustrate that biological groupings based on TMB and GEP biomarkers correlate with CD8 spatial location and activation state. Each subgroup has unique tumor immune features that can be related to immune resistance and warrant further investigation.

Impact of in ovo feeding of grape pomace extract on the growth performance, antioxidant status, and immune response of hatched broilers

Delivering natural antioxidants via in ovo feeding holds promise for enhancing the antioxidant status and performance of chickens. Therefore, The objective of this study was to evaluate the impacts of in ovo feeding during early embryonic development using grape pomace extract as a natural antioxidant on hatchability, productive performance, immune response, and antioxidant status broilers.. A total of 900 fertile broiler eggs from the Arbor Acres strain were utilized. Each egg was individually weighed, with egg weights ranging from 61.88±3 g. On the 17.5th day of incubation (DOI), the fertile eggs were divided into six groups. The first treatment group was untreated and designated as the control (C). The second group was the sham group (Sh), receiving a simulated injection. The third group, designated as the vehicle group (V), was injected with 100 µl of dimethyl sulfoxide (DMSO). The fourth group received an injection of 100 µl of grape pomace dissolved in DMSO at a concentration of 2 mg (T2). Similarly, the fifth and sixth groups were injected with 100 µl of grape pomace dissolved in DMSO at concentrations of 4 mg and 6 mg, (T4), (T6) respectively. Subsequently, all groups were raised under uniform conditions in terms of management, environment, and nutrition till five weeks of age. The grape pomace extract (GPE), obtained is rich in total phenolic content (16.07 mg/g), total flavonoid content (7.42 mg/g), and total anthocyanin (8.37 mg/g). GPE has exhibited significant antioxidant properties as evidenced by its effectiveness in DPPH scavenging and reducing power assays. Significant improvements in body weight at hatch were observed with in ovo feeding of grape pomace extract, particularly at the 4 mg level, surpassing the effectiveness of the 2 mg and 6 mg grape pomace levels, and this enhancement in body weight continued until the age of five weeks. GPE injection also led to a significant reduction in cholesterol levels, with the lowest levels recorded for the T4 group. Plasma total Antioxidant Capacity (TAC) levels were significantly elevated in groups treated with T4, T6, and T2 compared to the control group. Conversely, the control group showed a significant increase (P<0.01) in plasma malondialdehyde (MDA) levels. The immune response of hatched chicks from grape pomace extract-injected groups, especially the T4 group, exhibited improvement through increased IgM and IgG. These findings demonstrate that in ovo feeding of GPE, particularly at a dosage of 4 mg, enhances growth performance, immune response, and antioxidant status in hatched chicks. Thus, administering natural antioxidants, such as grape pomace extract, to developing broiler embryos via in ovo feeding could serve as a valuable strategy for enhancing the subsequent post-hatch productive performance, as well as bolstering the antioxidant and immunological status of broiler chicks.

Physiological and immunological assessment of two types of crayfish in aquaculture

Due to the need to develop domestic aquaculture of decapod crustaceans, one of the urgent issues is monitoring the health of these aquatic organisms through the most informative bioindicators — hemolymph indicators. The aim of the study was a comparative physiological and immunological assessment of long-toed (Pontastacus leptodactylus) and Australian red-clawed (Cherax quadricarinatus) river crayfish contained in a closed water use facility. The main hydrochemical parameters generally met the existing requirements. The physiological and immunological condition of crayfish was assessed by hematological and cytochemical analyses. Hemolymph samples were taken in vivo by puncture of the ventral sinus. The total number of hemocytes was determined in the native hemolymph in the Goryaev chamber. The number of cells in five large squares was counted. Lysosomal cationic protein was detected in hemocytes by the cytochemical reaction with bromophenol blue, which we previously modified. Red-clawed crayfish have a significantly 45% higher total number of hemocytes, which indicates its greater immune resistance to pathogens compared with long-toed crayfish. The most significant species differences in the hemogram were noted for agranulocytes (HC I) — in long-fingered crayfish, the indicator is higher with a high confidence coefficient (t). With a high degree of confidence, it is possible to judge a higher proportion of semigranulocytes (HC II) in red-lobed crayfish. The proportion of HC IV of long-fingered crayfish is greater than that of red-clawed crayfish. In red-clawed crayfish, the average cytochemical coefficient of ACC is lower than in long-fingered crayfish. This also confirms its high immune resistance due to the consumption of highly cytotoxic cationic protein in the process of immune protection.

Leukocyte Virus And Immunological Response Of The Body

This study examined the immunological condition of cattle infected with spontaneous leukosis. Specifically, it compared the levels of immunoglobulins in cattle infected with leukosis viruses from three different genera to those in healthy cattle. The moles in the experiment were vaccinated against protein illness to artificially stimulate their immune response. Significant alterations were noted in IgG2, and it was discovered that the distinction between breeds was hindered

Indicators of Immunological Status in Pregnant Women with Chronic Viral Hepatitis B and C

The work presents the results of a study of immunological indicators of cellular and humoral immunity in 45 pregnant women with chronic viral hepatitis B and C. Immunological parameters in pregnant women with CHB and CHC were characterized by suppression of the cellular component of immunity, which is manifested by a decrease in the number of total T-lymphocytes (CD3+), T-helpers (CD4+) and T-suppressors (CD8+), as well as natural killer cells (CD16), which is associated with the mechanism of maintaining pregnancy. Changes in humoral immunity are characterized by a moderate increase in the level of IgG and CEC; in case of CHC, relapse of the disease was also accompanied by an increase in class M immunoglobulins. Chronic viral hepatitis B and C in pregnant women leads to secondary immunodeficiency and an increase in the level of viral replication. A direct correlation has been revealed between indicators of the cellular immune response in CHB and CHC with the level of viral load, which must be taken into account when managing pregnancy.

The titers of antinuclear antibodies are associated with the degree of inflammation and organ damage in Primary Sjögren's Syndrome

Primary Sjögren’s Syndrome (pSS) falls within the category of connective tissue diseases, characterized by the presence of autoantibodies such as antinuclear antibodies (ANA). However, according to the classification criteria for pSS, some patients may exhibit a negative result for autoantibodies. Patients with a negative result for autoantibodies may lack typical features of connective tissue diseases, and the immunological state as well as the extent of organ involvement and damage may differ from those with positive autoantibodies. This study aims to compare the clinical phenotypes of patients with positive and negative autoantibodies, providing insights for disease classification and treatment selection for clinicians. Patients with pSS were grouped based on the presence and titers of their autoantibodies. Subsequently, differences in organ damage and laboratory indicators were compared between these groups, aiming to analyze the value of autoantibody titers in assessing the condition of pSS. (1) Patients with positive ANA exhibited elevated levels of inflammatory indicators, including ESR, IgG levels, lip gland biopsy pathology grade, and overall organ involvement, in comparison with patients with negative ANA (P < 0.05). Furthermore, ANA-positivity correlated with a higher occurrence of multi-organ damage, particularly affecting the skin, mucous membranes, and the hematological system (P < 0.05). (2) As ANA titers increased, patients demonstrated elevated levels of IgG and an escalation in organ involvement (P < 0.05). (3) Patients in the positive autoantibody group (positive for antinuclear antibodies, anti-SSA, or anti-SSB antibodies) had higher IgG levels compared to the negative group (P < 0.05). (4) Patients with positive anti-SSA and anti-SSB antibodies exhibited higher levels of inflammatory indicators and IgG compared to other patients (P < 0.05); however, no significant differences were observed in terms of organ involvement and organ damage. Patients with positive ANA in pSS typically exhibit higher levels of inflammation and an increased likelihood of experiencing multi-organ damage. Furthermore, as the ANA titers increase, both inflammation levels and the risk of multi-organ damage also escalate. Additionally, the presence of anti-SSA and anti-SSB antibodies may contribute to an elevated risk of increased inflammation levels, but does not increase the risk of organ damage.

Grape pomace in diets for European sea bass: influence on oxidative status, intestinal microbiota, and fillet quality

The use of intensive systems in aquaculture causes an increase in environmental stress agents, reducing water quality and facilitating the appearance of pathologies in individuals. In this context, the selection of ingredients is a key strategy in managing the quality of aquafeed and the cultivation of aquaculture species. Considering this, wine by-products can be a potential functional ingredient due to several particular characteristics, such as their low cost, large volumes produced, and for being a natural source of bioactive compounds with antioxidant activity. The present study developed different experiments focused on evaluating the benefits of feeding juvenile European sea bass during 5 weeks with feeds incorporating 0.4% red wine grape pomace (GP). At the end of the feeding period, potential modifications in metabolism, immunological and oxidative status, and functionality of intestinal microbiota were assessed as well as the potential protective effect against oxidation in fish fillets during 6 days of cold storage (4 °C). In addition, the preservative effect of GP on the feed when stored for a period of 12 weeks at two different temperatures (4 °C and 25 °C) was evaluated. The results demonstrated that the inclusion of GP in feeds for European sea bass prevents oxidation when stored at room temperature. In addition, a general improvement in the physiological and immunological status, as well as fillet quality, was evidenced.

The chronic leukocyte and inflammatory cytokine responses of older adults to resistance training in normobaric hypoxia; a randomized controlled trial

Trial designOlder adults experience chronic dysregulation of leukocytes and inflammatory cytokines, both at rest and in response to resistance training. Systemic hypoxia modulates leukocytes and cytokines, therefore this study characterized the effects of normobaric hypoxia on the leukocyte and cytokine responses of older adults to resistance training.Methods20 adults aged 60–70 years performed eight weeks of moderate-intensity resistance training in either normoxia or normobaric hypoxia (14.4% O2), consisting of two lower body and two upper body exercises. Venous blood was drawn before and after the training intervention and flow cytometry was used to quantify resting neutrophils, lymphocytes, monocytes, eosinophils and basophils, in addition to the subsets of lymphocytes (T, B and natural killer (NK) cells). Inflammatory cytokines were also quantified; interleukin 1 beta (IL-1β), IL-4, IL-6, IL-8, IL-10 and tumor necrosis factor alpha (TNF-α). Acute changes in leukocytes and cytokines were also measured in the 24 h following the last training session.ResultsAfter the intervention there was a greater concentration of resting white blood cells (p = 0.03; 20.3% higher) T cells (p = 0.008; 25.4% higher), B cells (p = 0.004; 32.6% higher), NK cells (p = 0.012; 43.9% higher) and eosinophils (p = 0.025; 30.8% higher) in hypoxia compared to normoxia, though the cytokines were unchanged. No acute effect of hypoxia was detected in the 24 h following the last training session for any leukocyte population or inflammatory cytokine (p < 0.05).ConclusionsHypoxic training caused higher concentrations of resting lymphocytes and eosinophils, when compared to normoxic training. Hypoxia may have an additional beneficial effect on the immunological status of older adults.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR). Trial number: ACTRN12623001046695. Registered 27/9/2023. Retrospectively registered. All protocols adhere to the COSORT guidelines.

Analysis of the immunological response to antiviral therapy in patients with different subtypes of HIV/AIDS: a retrospective cohort study

ObjectiveTo evaluate the effectiveness of standardised antiretroviral therapy (ART) among different HIV subtypes in people living with HIV/AIDS (PLWHA), and to screen the best ART regimen for this patient population.DesignA...

Molecular Changes in Immunological Characteristics of Bone Marrow Multipotent Mesenchymal Stromal Cells in Lymphoid Neoplasia.

Immune system and bone marrow stromal cells play an important role in maintaining normal hematopoiesis. Lymphoid neoplasia disturbs not only development of immune cells, but other immune response mechanisms as well. Multipotent mesenchymal stromal cells (MSCs) of the bone marrow are involved in immune response regulation through both intercellular interactions and secretion of various cytokines. In hematological malignancies, the bone marrow stromal microenvironment, including MSCs, is altered. Aim of this study was to describe the differences of MSCs' immunological function in the patients with acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). In ALL, malignant cells arise from the early precursor cells localized in bone marrow, while in DLBCL they arise from more differentiated B-cells. In this study, only the DLBCL patients without bone marrow involvement were included. Growth parameters, surface marker expression, genes of interest expression, and secretion pattern of bone marrow MSCs from the patients with ALL and DLBCL at the onset of the disease and in remission were studied. MSCs from the healthy donors of corresponding ages were used as controls. It has been shown that concentration of MSCs in the bone marrow of the patients with ALL is reduced at the onset of the disease and is restored upon reaching remission; in the patients with DLBCL this parameter does not change. Proliferative capacity of MSCs did not change in the patients with ALL; however, the cells of the DLBCL patients both at the onset and in remission proliferated significantly faster than those from the donors. Expression of the membrane surface markers and expression of the genes important for differentiation, immunological status maintenance, and cytokine secretion differed significantly in the MSCs of the patients from those of the healthy donors and depended on nosology of the disease. Secretomes of the MSCs varied greatly; a number of proteins associated with immune response regulation, differentiation, and maintenance of hematopoietic stem cells were depleted in the secretomes of the cells from the patients. Lymphoid neoplasia leads to dramatic changes in the functional immunological status of MSCs.

The inflammatory immunity and gut microbiota are associated with fear response differences in laying hens

The fear response is a crucial adaptive mechanism for coping with environmental changes, and the individuals have different levels of fearfulness. The purpose of this study was to determine the status of the immune response and gut health in hens with different fear responses. A total of 80 healthy 75-week-old native Lindian chickens were individually housed in conventional cages and categorized into high (TH) and low (TL) levels of fearfulness using the tonic immobility (TI) test. The immunological status and intestinal health of the laying hens were assessed, and the intestinal microbial community was sequenced using 16S rRNA testing. The results showed that the immune-related genes of interleukin (IL)-1β, IL-4, IL-6, and IgG were significantly upregulated in the spleen of TH hens compared with hens in the TL group (P < 0.01). The inflammatory immune-related genes Toll-like receptor (TLR)2, TLR4, nuclear factor (NF)-κB, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, IL-10, and IgG were significantly increased in the intestinal tract, whereas IL-4, IgA, and the intestinal barrier gene claudin-4 were significantly decreased in TH hens (P < 0.05). In addition, serum concentrations of IL-1β, IL-6, IL-10, interferon (IFN)-α and IgG were significantly higher in TH hens (P < 0.01). A high fear response also led to changes in gut microbial diversity, with a higher Simpson's index and lower β-diversity similarity than hens with a low-fear response (P < 0.05). The TH group showed an increase in eight genera, including Bacillaceae and Coprococcus, whereas the genus Anaerorhabdus decreased (P < 0.05). The gut microbiota has also been associated with gut barrier genes, and inflammatory cytokines. Bartonella stimulates IL-1β and IgG secretion, whereas Lactobacillus inhibits IL-6 secretion, and Coprococcus and Subdoligranulum are associated with the maintenance of intestinal barrier function. The results of this study suggest that laying hens with high fear response levels have a more sensitive immune response and a more enriched gut microbiota, which may have positive effects on adapting to a complex environment.

Immunological structure and yield of winter rye varieties bred by the Federal Agricultural Research Center of the North-East named N. V. Rudnitsky

The study was carried out in the conditions of Kirov region in 2019–2023. Against provocative and infectious backgrounds of snow mold, root rot, ergot, powdery mildew, leaf and stem rust, the immunological state and yield of 15 varieties of winter rye created over a 73-year period were studied. Taking into account the breeding methods, the source material used and the year of creation, they were conditionally distributed over five successive periods of breeding and variety change: I – Vyatka 2, Kirovskaya 89; II – Falenskaya 4, Snezhana, Rushnik; III – Flora, Grafinya, Batist; IV – Lika, Talitsa; V – Symphoniya, Garmoniya, Graphit, Graphit FP, Perepel. When recording diseases, well-known methods were used. Research has shown that as a result of breeding, on artificial infectious backgrounds newly created varieties showed a decrease in the development of root rot (Flora, Perepel, Garmoniya – degree of damage 14.6, 15.5 and 15.0 %) and ergot (Flora, Grafinya, Batist, Lika, Symphoniya, Graphit FP, Garmoniya – damage 11.4...15.9 %), grain contamination with sclerotia – 0.38...1.84 %. In varieties of the I period of breeding the degree of root rot infection was 18.8 %, ergot infection – 31.7 %. There is no progress in breeding for resistance to powdery mildew and rust types. The most productive varieties are Lika and Batist (769.3 and 738.7 g/m2), which significantly exceed the Falenskaya 4 standard (578.8 g/m2). A close and significant dependence (p ≥ 095) was revealed between the yield of winter rye varieties and regrowth of plants after snow mold infection (r = 0.693...0.830) as well as grain contamination with sclerotia (r = -0.531...-0.712). The relationship between the yield of winter rye and the development of other studied diseases is insignificant and weak. Considering the high harmfulness of snow mold and ergot in the research region, it is necessary to continue to carry out breeding improvement of varieties for these characteristics, as well as to increase resistance to powdery mildew and types of rust.

Usefulness of the C-Reactive Protein (CRP)-Albumin-Lymphocyte (CALLY) Index as a Prognostic Indicator for Patients With Gastric Cancer.

The C-reactive protein (CRP)-albumin-lymphocyte (CALLY) index is a novel immune nutrition scoring system associated with cancer prognosis. This study investigated the association between the CALLY index and the long-term outcomes of patients with gastric cancer. We included 175 patients with gastric cancer who underwent curative gastrectomies at the Department of Surgery, International University of Health and Welfare Hospital between January 2011 and October 2019. The CALLY index was calculated based on the levels of serum albumin, serum CRP, and peripheral lymphocyte count. Utilizing both univariate and multivariate analyses, the prognostic value of the CALLY index was investigated. In the multivariate analyses, disease stage (hazard ratio [HR], 7.85; 95% confidence interval [CI], 3.31-18.6; P < .01), microvascular invasion (HR, 2.88; 95% CI, 1.30-6.36; P < .01), and low CALLY index (HR, 2.18; 95% CI, 1.00-4.76; P = .05) were independent and significant predictors of disease-free survival. Low body mass index (HR, 4.15; 95% CI, 1.63-10.6; P < .01), advanced disease stage (HR, 8.22; 95% CI, 3.47-19.5; P < .01), and low CALLY index (HR, 3.00; 95% CI, 1.3-6.93; P = .01) were independent and significant predictors of overall survival. The low CALLY index group had a lower body mass index (P < .01), advanced disease stage (P < .01), and a higher Glasgow prognostic score (P < .01). The CALLY index may be associated with a poor prognosis for gastric cancer, highlighting the utility of a comprehensive assessment using inflammatory, nutritional, and immunological statuses.

Antimicrobial peptide LL37 and regulatory T cell associated with late-onset sepsis in very preterm infants

Stem cell therapy may prevent late-onset sepsis (LOS) via antimicrobial peptide LL37 secretion and regulatory Tcell (Treg) regulation. The early prediction of LOS is still a challenge. This study evaluated whether immunological state of LL37 or Tregs precedes LOS. We firstly analyzed the LL37 level, Treg proportion, and LOS incidence in very preterm infants treated with autologous cord blood mononuclear cells (ACBMNCs) in our previous trial. Then, we constructed a prediction model and built validation cohort. We found ACBMNC intervention reduced the incidence of LOS from 27.3% to 6.9% (p= 0.021). LL37 and Treg abundances were higher in the ACBMNCs group. The nomogram demonstrated that early-life Treg and LL37 characteristics were closely associated with LOS (area under the curve, AUC 0.936), with implications for early prediction and timely clinical management. This composite model was also helpful to evaluate the beneficial effect of ACBMNCs intervention on LOS, thus promoting translational research.

Spontaneous regression of brain tumors in children: case report and literature review

Introduction: They are defined as space-occupying lesions that present radiological characteristics of tumors and that resolve spontaneously during radiological follow-up. Spontaneous regression of tumors is a rare phenomenon, with a regression rate in malignant tumors of 1/60,000 to 100,000 patients. Materials and Methods: An 11-year-old female with polydipsia, polyuria, 5 kg weight loss, ataxia, headache, vision loss, and diabetes insipidus. CT with chiasm-dependent tumor occupying the interpenduncular cistern, displacing the hypothalamus ventrally. Results: An excisional biopsy was performed using a pterional approach, microsurgical resection + ultrasonic aspiration, during the trans-surgical procedure thickening of the chiasm and optic nerves was found. WHO Grade I Pilocytic Astocytoma was reported. In the two-year follow-up with magnetic resonance imaging of the brain, we observed complete tumor regression. Discussion: Partial cytoreduction of the tumor, biopsy, radiotherapy or chemotherapy play a role in the initiation of tumor apoptosis. Surgical trauma favorably alters the biological activity of the tumor and the immunological status of the host. Conclusions: The mechanisms of spontaneous regression and spontaneous involution of residual tumor after surgery are not known. Apoptosis may be the common denominator, possible mechanisms include immunological, genetic and biological factors.

Evaluation of the Epstein–Barr virus occurrence at the present stage (literature review)

The purpose of this article is to review and analyze the foreign and domestic scientific papers to assess the Epstein-Barr virus (EBV) occurrence in the human population. &#x0D; A search of Russian and foreign publications in the PubMed and E-library databases was conducted. The high ecological and medical significance &#x0D; of EBV-infection is due to its global spread in the human population, lifelong persistence of EBV in the human body. Evidence has been collected EBV to be involved in the development of various somatic pathologies, such as rheumatic diseases and vasculitis, chronic kidney disease, cardiovascular pathologies, pathologies of the gastrointestinal tract, T- and B-cell lymphomas in children and adults, nasopharyngeal carcinoma. These diseases are the main causes of population disability and premature death not only in Russia, but also in the World. The deterioration of the ecological and epidemic situation for &#x0D; EBV-infection is associated with the other infectants spread that change the population immunological status. These include the human immunodeficiency virus, hepatitis B and C viruses, SARS-CoV-2, Mycobacterium tuberculosis. With the simultaneous persistence of these infectants, their synergistic or antagonistic effect on the human body occurs. In the modern World, the COVID-19 and the EBV-infection are simultaneously developing. It is difficult to say which infection is more significant in terms of medical, social. and economic losses of the human population. The EBV has been undeservedly given little attention. &#x0D; It is necessary to optimize preventive measures and epidemic surveillance for EBV-infection.

New insights into Trypanosoma cruzi genetic diversity, and its influence on parasite biology and clinical outcomes.

Chagas disease, caused by Trypanosoma cruzi, remains a serious public health problem worldwide. The parasite was subdivided into six distinct genetic groups, called "discrete typing units" (DTUs), from TcI to TcVI. Several studies have indicated that the heterogeneity of T. cruzi species directly affects the diversity of clinical manifestations of Chagas disease, control, diagnosis performance, and susceptibility to treatment. Thus, this review aims to describe how T. cruzi genetic diversity influences the biology of the parasite and/or clinical parameters in humans. Regarding the geographic dispersion of T. cruzi, evident differences were observed in the distribution of DTUs in distinct areas. For example, TcII is the main DTU detected in Brazilian patients from the central and southeastern regions, where there are also registers of TcVI as a secondary T. cruzi DTU. An important aspect observed in previous studies is that the genetic variability of T. cruzi can impact parasite infectivity, reproduction, and differentiation in the vectors. It has been proposed that T. cruzi DTU influences the host immune response and affects disease progression. Genetic aspects of the parasite play an important role in determining which host tissues will be infected, thus heavily influencing Chagas disease's pathogenesis. Several teams have investigated the correlation between T. cruzi DTU and the reactivation of Chagas disease. In agreement with these data, it is reasonable to suppose that the immunological condition of the patient, whether or not associated with the reactivation of the T. cruzi infection and the parasite strain, may have an important role in the pathogenesis of Chagas disease. In this context, understanding the genetics of T. cruzi and its biological and clinical implications will provide new knowledge that may contribute to additional strategies in the diagnosis and clinical outcome follow-up of patients with Chagas disease, in addition to the reactivation of immunocompromised patients infected with T. cruzi.

Molecular subtyping and the construction of a predictive model of colorectal cancer based on ion channel genes

PurposeColorectal cancer (CRC) is a highly heterogeneous malignancy with an unfavorable prognosis. The purpose of this study was to address the heterogeneity of CRC by categorizing it into ion channel subtypes, and to develop a predictive modeling based on ion channel genes to predict the survival and immunological states of patients with CRC. The model will provide guidance for personalized immunotherapy and drug treatment.MethodsA consistent clustering method was used to classify 619 CRC samples based on the expression of 279 ion channel genes. Such a method was allowed to investigate the relationship between molecular subtypes, prognosis, and immune infiltration. Furthermore, a predictive modeling was constructed for ion channels to evaluate the ion channel properties of individual tumors using the least absolute shrinkage and selection operator. The expression patterns of the characteristic genes were validated through molecular biology experiments. The effect of potassium channel tetramerization domain containing 9 (KCTD9) on CRC was verified by cellular functional experiments.ResultsFour distinct ion channel subtypes were identified in CRC, each characterized by unique prognosis and immune infiltration patterns. Notably, Ion Cluster3 exhibited high levels of immune infiltration and a favorable prognosis, while Ion Cluster4 showed relatively lower levels of immune infiltration and a poorer prognosis. The ion channel score could predict overall survival, with lower scores correlated with longer survival. This score served as an independent prognostic factor and presented an excellent predictive efficacy in the nomogram. In addition, the score was closely related to immune infiltration, immunotherapy response, and chemotherapy sensitivity. Experimental evidence further confirmed that low expression of KCTD9 in tumor tissues was associated with an unfavorable prognosis in patients with CRC. The cellular functional experiments demonstrated that KCTD9 inhibited the proliferation, migration and invasion capabilities of LOVO cells.ConclusionsIon channel subtyping and scoring can effectively predict the prognosis and evaluate the immune microenvironment, immunotherapy response, and drug sensitivity in patients with CRC.

Chitosan-LeoA-DNA Nanoparticles Promoted the Efficacy of Novel LeoA-DNA Vaccination on Mice Against Helicobacter pylori.

More than half of the world's population is infected with Helicobacter pylori (H. pylori), which may lead to chronic gastritis, peptic ulcers, and stomach cancer. LeoA, a conserved antigen of H. pylori, aids in preventing this infection by triggering specific CD3+ T-cell responses. In this study, recombinant plasmids containing the LeoA gene of H. pylori are created and conjugated with chitosan nanoparticle (CSNP) to immunize BALB/c mice against the H. pylori infection. We used the online Vaxign tool to analyze the genomes of five distinct strains of H. pylori, and we chose the outer membrane as a prospective vaccine candidate. Afterward, the proteins' immunogenicity was evaluated. The DNA vaccine was constructed and then encapsulated in CSNPs. The effectiveness of the vaccine's immunoprotective effects was evaluated in BALB/c mice. Purified activated splenic CD3+ T cells are used to test the anticancer effects in vitro. Nanovaccines had apparent spherical forms, were small (mean size, 150-250 nm), and positively charged (41.3 ± 3.11mV). A consistently delayed release pattern and an entrapment efficiency (73.35 ± 3.48%) could be established. Compared to the non-encapsulated DNA vaccine, vaccinated BALB/c mice produced higher amounts of LeoA-specific IgG in plasma and TNF-α in splenocyte lysate. Moreover, BALB/c mice inoculated with nanovaccine demonstrated considerable immunity (87.5%) against the H. pylori challenge and reduced stomach injury and bacterial burdens in the stomach. The immunological state in individuals with GC with chronic infection with H. pylori is mimicked by the H. pylori DNA nanovaccines by inducing a shift from Th1 to Th2 in the response. In vitro human GC cell development is inhibited by activated CD3+ T lymphocytes. According to our findings, the H. pylori vaccine-activated CD3+ has potential immunotherapeutic benefits.