Secretory Immunity Research Articles

Delving the depths of 'terra incognita' in the human intestine - the small intestinal microbiota.

The small intestinal microbiota has a crucial role in gastrointestinal health, affecting digestion, immune function, bile acid homeostasis and nutrient metabolism. The challenges of accessibility at this site mean that our knowledge of the small intestinal microbiota is less developed than of the colonic or faecal microbiota. Here, we summarize the features and fluctuations of the microbiota along the small intestinal tract, focusing on humans, and discuss physicochemical factors and assessment methods, including the technical challenges of investigating the low microbial biomass of the proximal small bowel. We highlight the essential protective mechanisms of the small intestine, including motility, the paracellular barrier and mucus, and secretory immunity, to show their roles in limiting excessive exposure of host tissues to microbial metabolites. We address current knowledge gaps, particularly the variability among individuals, the effects of dysbiosis of the small intestinal microbiota on health and how different taxa in small intestinal microbiota could compensate for each other functionally.

Abstract SoA2-01: Cellular senescence: The senescence-associated secretory phenotype (SASP) and immunity

Abstract Cellular senescence is a stress-induced program following aberrant oncogene activation or administration of cancer therapies, including chemotherapeutic agents and CDK4/6 inhibitors commonly used for treating advanced breast cancers, that results in the proliferative arrest of damaged cells and induction of the senescence associated secretory phenotype (SASP). The SASP involves secretion of inflammatory cytokines and chemokines and upregulation of immunomodulatory cell surface molecules on senescent cells that can promote their clearance by the immune system and tumor resolution. However, if left unchecked, the chronic SASP can also lead to immune suppression and further tissue damage that drives tumor dissemination and metastasis. Here we will discuss our efforts to understand how the SASP can promote anti-tumor immunity and immunotherapy activity in some cancer contexts yet in others immune suppression and tumor promotion. Our findings in other solid tumor contexts demonstrate that the tissue microenvironment has a profound impact of the type of SASP program activated and SASP-mediated immune responses produced and suggest further therapeutic interventions to remodel the SASP for immune control of cancer. Moreover, our results in other hormone-driven cancers suggest that CDK inhibitor and chemotherapy regimens produce different SASPs and resulting effects on myeloid cell and lymphocyte phenotypes that could explain their varying effects on anti-tumor immunity and treatment outcomes. Collectively these findings have important implications for breast cancer treatment and pave the path for rationale combination therapies with senescence-inducing agents to achieve immune control in breast and other immunologically “cold” solid tumor malignancies that are generally unresponsive to current immunotherapy regimens. Citation Format: M. Ruscetti. Cellular senescence: The senescence-associated secretory phenotype (SASP) and immunity [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr SoA2-01.

Influence of using a domestic adhesive cream for fixation of removable dentures with plantain extract on mucosal microbiome and secretory immunity of the mouth

Relevance. Denture stomatitis, including fungal infection, which affects many wearers of removable dental prostheses, has a multifactorial etiology with poor oral hygiene as the main predisposing factor. Therefore, the search for means that contribute to the prevention of occurrence and elimination of denture stomatitis in persons using removable dental prostheses remains relevant.Objective. The effect of the adhesive cream for fixation of dentures Asepta Рarodontal with plantain extract on the mucosal microbiome and secretory immunity of the mouth of patients using removable dentures was evaluated.Materials and Methods. The content of secretory immunoglobulin A (sIgA) in saliva was studied by enzyme-linked immunosorbent assay and microbiological examination for periodontopathogens (Prevotella intermedia, Bacteroides forsythus, Treponema denticola, Actinobacillus actinomycetemcomitans, Porhyromonas gingivalis), as well as Streptococccus spp, Staphylococcus spp and Candida spp in 3 groups of patients who did not use any dental prostheses (1 control group, 30 people). ), as well as those who were made partial removable acrylic dentures from the first day of application were offered to use domestic adhesive cream for fixation of dentures Asepta Рarodonta (2 main group, 30 people) and who were made partial removable acrylic dentures, but their adaptation period and subsequent use of dentures passed without the use of any adhesive means for fixation of dentures (3 comparison group, 30 people).Results. It was found that after 6 months of application of adhesive cream for fixation of dentures with plantain extract there was a significant decrease in detection of Bacteroides forsythus and Porphyromonas gingivalis in comparison with the control group, as well as a significant increase in the level of sIgA, which was noted 1 month after the beginning of application of Asepta Carodontal denture fixation agent and continued after 6 months. This indicates the strengthening of secretory immunity, which leads to increased binding of microbes in saliva with their further excretion, inhibition of adhesion of C. albicans to the walls of the denture and epithelial cells of the oral mucosa, which ultimately contributes to a decrease in colonization of the oral mucosa epithelium by fungi and a decrease in the incidence of stomatitis.Conclusion. Prevention of denture stomatitis by optimizing the microbiome of the oral mucosa and mucosal immunity is possible due to the use of adhesive cream for fixation of dentures Asepta Carodontal, as it creates the possibility of preserving and optimizing the microbiocenosis and immune balance in the oral cavity after dental prosthetics, which allow us to recommend the use of adhesive agents for fixation of removable dental prostheses, including cream Asepta Carodontal.

Cytotoxicity of Sodium Bicarbonate Solution to Human Gingival Fibroblast Cells

Immunoglobulin A (IgA) is a crucial antibody originating in mucosal lymphoid tissue, actively distributed across the epithelium. It plays a vital role in binding to and neutralizing microbes that threaten organisms through mucosal organs, thereby contributing to mucosal or secretory immunity. This research aims to determine the Cytotoxicity of Sodium Bicarbonate Solution to Human Gingival Fibroblast Cells. The research method used to investigate the safety and efficacy of various sodium bicarbonate concentrations, we conducted a laboratory experimental study utilizing a post-test-only control group design. Sodium bicarbonate solutions with concentrations of 1%, 2%, 3.5%, 7%, 10%, 15%, and 20% were tested. The results of the study using analysis through ANOVA followed by Tukey HSD revealed that solutions with concentrations of 20%, 15%, and 10% exhibited comparable non-toxicity to fibroblast cells, as they shared the same column. In contrast, concentrations of 7%, 3.5%, 2%, and 1% were found to have toxicity levels that exceeded the IC50 threshold. Further examination using the Tukey HSD test showed that the 2% and 3.5% concentration groups did not show significant differences. In conclusion, the Sodium bicarbonate solutions with concentrations of 7%, 3.5%, 2%, and 1% are not toxic to fibroblast cells and can be used as a basis for further research applications based on sodium bicarbonate materials. It is recommended for future studies to conduct further examinations with different concentrations.

Seasonal changes in secretory immunity indices in saliva in indigenous and alien inhabitants of the Yakutia Arctic zone

Introduction. The combination of extreme climate with intensive migration processes creates favourable conditions for the spread of infectious diseases in the Arctic zone of the Russian Federation. 
 The purpose of the study: comparative analysis of immunity indicators in saliva samples of indigenous and alien residents of Yakutia Arctic zone, taking into account the influence of seasonal factors. 
 Materials and methods. Samples of mixed saliva of indigenous (n=212) and alien (n=120) male residents from Chokurdakh and Tiksi settlements were taken in 4 batches corresponding to the seasonal transition from summer to early winter. Levels of secretory IgA (sIgA) and cytokines IL-1ß, IL-8 and IL-6 in saliva were determined by ELISA. Main Effects ANOVA was used for the data analysis. 
 Results. No significant age-related changes of the indicators were found. During the transition from summer to winter, there was a decrease in sIgA, IL-1ß, and IL-8 levels in saliva of the examined persons (p from 0.001 to 1.6•10–7). Rate of seasonal changes did not differ between indigenous and alien inhabitants. IL-6 level in saliva of Chokurdakh residents (200 km from the sea) was higher (F(1,139)=9,202; p=0.003) and sIgA level was lower (F(1,324)=3,560; p=0.060) than corresponding levels in residents of coastal settlement Tiksi. Comparison of the body mass indices (medians 24.3 in Chokurdakh and 26.2 in Tiksi, p=0.0005) confirms that it may be the result of inequality in physical activity of residents due to almost 2-fold increase in wind speed and precipitation in Tiksi. 
 Limitations. Monitoring period till the beginning of winter, and not later, could predetermine the absence of the expected differences between indigenous (evolutionarily adapted) and alien residents. 
 Conclusion. Evaluation of immunity indicators in saliva samples is a simple and informative approach to study mechanisms of human adaptation to extreme climatic conditions.

Study of the safety and immunogenicity of VLP-based vaccine for the prevention of rotavirus infection in neonatal minipig model

In Russia, almost half of the cases of acute intestinal infections of established etiology in 2022 are due to rotavirus infection (RVI). There is no specific treatment for rotavirus gastroenteritis. There is a need to develop modern, effective and safe vaccines to combat rotavirus infection that are not capable of multiplying (replicating) in the body of the vaccinated person. A promising approach is to create vaccines based on virus-like particles (VLPs). Study of the safety and immunogenicity of a vaccine against rotavirus infection based on virus-like particles of human rotavirus A in newborn minipigs with multiple intramuscular administration. Newborn minipigs were used as an animal model in this study. The safety of the tested vaccine was assessed based on thermometry data, clinical examination, body weight gain, clinical and biochemical blood parameters, as well as necropsy and histological examination. When studying the immunogenic properties of the Gam-VLP-rota vaccine in doses of 30 and 120 µg, the cellular, humoral and secretory immune response was studied. The results of assessing the general condition of animals during the immunization period, data from clinical, laboratory and pathomorphological studies indicate the safety of the vaccine against human rotavirus infection based on VLP (Gam-VLP-rota) when administered three times intramuscularly. Good local tolerance of the tested vaccine was demonstrated. The results of the assessment of humoral immunity indicate the formation of a stable immune response after three-time immunization with Gam-VLP-rota, stimulation of the production of antigen-specific IgG antibodies and their functional activity to neutralize human rotavirus A. It was shown that following the triple immunization with the minimum tested concentration of 30 µg/dose, animals developed a cell-mediated immune response. The results of the IgA titer in blood serum and intestinal lavages indicate the formation of both a systemic immunological response and the formation of specific secretory immunity to human rotavirus A. Thus, three-time intramuscular immunization of minipigs with the Gam-VLP-rota vaccine forms stable protective humoral and cellular immunity in experimental animals. Evaluated vaccine is safe and has good local tolerability.

Progress and emerging strategies to preserve function in the treatment of sinonasal cancer.

The sinonasal structures and their adjacent organs host several functions including vision, olfaction, nasal respiration and filtration, secretory immunity, facial expression, articulation, and oral deglutition. We reviewed the current evidence supporting functional preservation in sinonasal cancer treatment. Primary surgery with or without adjuvant modalities continues to be the standard of care for sinonasal cancer. Unfortunately, functional compromise remains a dominant negative feature of this approach. More recently, through advances in therapeutic techniques and improved understanding of the relevant tumor biology, treatments aimed at preserving function and cosmesis are emerging. The evidence for such progress involving minimal access surgery, surgical reconstruction for rehabilitation, new techniques in radiation therapy, inclusion of systemic and locally enhanced chemotherapy, and therapeutic agents based on molecular targets are highlighted. This multi-prong approach bodes well for future patients with sinonasal cancer to undergo successful treatment that includes maximal preservation of associated functions.

Professional Athletes Maintain High TNF-Alpha or IFN-Gamma Related Inflammatory Status after Recovering from COVID-19 Infection without Developing a Neutralizing Antibody Response

Introduction: Professional athletes are endangered by COVID-19 and belong to the high-risk population due to their lifestyle. To obtain information on the behavior of COVID-19 in professional athletes, serological, cytokine, and virus neutralization capacities were analyzed. Materials and methods: Hungarian national teams participated in international sports events during the early phases of the COVID-19 epidemic in 2020. Altogether, 29 professional athletes volunteered to donate plasma. Their serological status was evaluated by IgA, IgM, and IgG ELISAs and the highest virus neutralization titer in an in vitro live tissue assay. Plasma cytokine patterns were analyzed with a Bioplex multiplex ELISA system. Results: Surprisingly, only one athlete (3%) had anti-SARS-CoV-2 IgG, while IgA was more common (31%). Neither plasma showed direct virus neutralization in a titer over 1:10; hence, they were not suitable for reconvalescent treatment. The ‘cytokine storm’ markers IL-6 and IL-8 were at baseline levels. In contrast, either the TNF-alpha-related cytokines or the IFN-gamma-associated cytokines were elevated. There was a strong negative correlation between the TNF-alpha- or IFN-gamma-related cytokines. Conclusions: Professional athletes are susceptible to the SARS-CoV-2 infection without developing long-term immunity through neutralizing immunoglobulins. Elevated secretory and cellular immunity markers indicate that these systems are probably responsible for virus elimination in this subpopulation.

Effects of acrylic dentures on oral mucosa and salivary antimicrobial peptide content in denture wearers

Relevance. Aging of the body leads to the development of an imbalance in the secretory immunity of the oral mucosa, with the loss of natural teeth leading to an even more rapid decline in the host’s oral defense reactions. However, studies on salivary antimicrobial peptides in denture users and their potential role in protecting against the development of inflammation are still scarce at this time.Purpose. To evaluate the effects of full removable acrylic dentures on the oral mucosa and analyze the content of antimicrobial peptides in the saliva of wearers of such dentures.Materials and methods. Sixty-seven (21 men and 46 women) elderly patients (61 to 74 years old) with complete tooth loss were examined and divided into 3 study groups. In the 1st control group the patients did not use any dentures. Patients in groups 2 and 3 were made full removable acrylic dentures for the upper and lower jaws, and in group 2 from the first day of the adaptation period was used domestic denture fixation cream ASEPTA PARODONTAL. Assessment of the denture bed on the hard palate was performed visually using the Schiller – Pisarev test. Microbiological examination for Candida albicans was performed by PCR-diagnostics. The content of antimicrobial peptides in saliva was assessed using ELISA kits by Hycult Biotech.Results. The use of the adhesive cream was found to improve the condition of the palatal mucosa by 25% on the 15th day and by 50% on the 30th day of the adaptation period. Candida albicans was detected in oral material in more than 55% of patients in all groups during their initial examination. In the group of patients using denture fixation cream, a significant decrease in Candida albicans carriage was noted, while an increase in Candida albicans detection of up to 70% was noted in those not using the cream. There was also an increase in the level of cathelicidin LL-37 in the saliva of patients without the use of the cream and with a marked increase in inflammation. One month after dentures in patients without cream use the content of alpha-defensins (HNP 1-3) was significantly lower than that of the group with cream and the control group.Conclusion. On the basis of the carried out clinical and laboratory study, the domestic ACEPTA adhesive cream should be recommended for optimization of the adaptation period to removable acrylic dentures as well as for their permanent use.

Changes in mucosal immunity of oral cavity upon tooth loss in patients with periodontal diseases

Partial or complete loss of teeth occurs in elderly and senile people, caused, mainly, by chronic generalized periodontitis. At the same time, the impact of presence or absence of persisting teeth and periodontium, is practically not covered in the literature as a factor of balance in the oral cavity, including local immunity of the mucous membranes. Our work concerned the changes in local immunity of the oral cavity occuring with the loss of natural teeth. We have observed 45 elderly people who were divided into 3 study groups, i.e., without inflammatory periodontal pathology (1), with periodontitis (2) and with chronic periapical inflammatory processes in the absence of periodontal inflammation (3). In order to sanitize oral cavity before the upcoming dental prosthetics, the patients of study groups 2 and 3 underwent extraction of all teeth in the upper and lower jaws. Indices of local immunity of the oral cavity in the salivary fluid of patients were assessed before surgical sanitation of the oral cavity (before the teeth extraction) and 30-35 days after removal of the last tooth. We have measured the salivary levels of secretory immunoglobulin A (sIgA) as well as pro-inflammatory cytokines, i.e., interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor- (TNF), and anti-inflammatory cytokines, e.g., receptor antagonist of interleukin-1 (RAIL), interleukin-4 (IL-4), interleukin-10 (IL-10)), as well as contents of antimicrobial peptides in saliva (catelicidin LL-37 and alphadefensins 1-3 (HNP1-3). We have found that the development of inflammation in severe inflammatory periodontal diseases, in particular, chronic generalized periodontitis requiring tooth extraction for oral cavity sanitation is characterized by functional insufficiency of secretory immunity of the oral mucosa associated with decreased secretion of secretory immunoglobulin A and antimicrobial peptides of neutrophilic origin, as well as a shift in the salivary cytokine balance towards increased production of pro-inflammatory cytokines. Removal of teeth, as the main source of inflammation and the basis for maintenance of dysbiotic microbiome biofilm leads to elimination of inflammation and the restoration of immune balance in the oral cavity.

Analysis of Saliva and Gingival Crevicular Fluid Immunoglobulin A in Adults Having Different Caries Status

Objective: The aim of the study was to compare the salivary IgA and gingival crevicular fluid IgA levels in caries active and caries free subjects. Methods: The study was carried out on 40 subjects divided into two groups, Group I caries free, (DMFT =0) and Group II caries active, (DMFT >10). Saliva and gingival crevicular fluid samples were obtained and plaque index, gingival index, gingival crevicular fluid volume and salivary flow rate were determined. The levels of S. mutans and lactobacillus were determined by culture. IgA concentrations of saliva and gingival crevicular fluid samples were determined using the ELISA. Data were analyzed using the Mann-Whitney U and χ2 tests (α = 0.05). Results: Gingival crevicular fluid volume, plaque index and gingival index values of group II were significantly higher than group I (p< 0.05). Although lactobacillus counts of group II were higher than group I, no statistically significant differences were observed for microorganism counts (p>0.05). Salivary flow rate, gingival crevicular fluid-IgA and saliva-IgA levels were no statistically significant between the groups (p>0.05). Conclusion: The present study showed that microorganism counts in the saliva did not by themselves influence the DMFT index. There is no dependence between secretory immunity and dental caries in subjects.

Exogenous and Endogenous Triggers Differentially Stimulate Pigr Expression and Antibacterial Secretory Immunity in the Murine Respiratory Tract

PurposeTransport of secretory immunoglobulin A (SIgA) through the airway epithelial cell barrier into the mucosal lumen by the polymeric immunoglobulin receptor (pIgR) is an important mechanism of respiratory mucosal host defense. Identification of immunomodulating substances that regulate secretory immunity might have therapeutic implications with regard to an improved immune exclusion.Thus, we sought to analyze secretory immunity under homeostatic and immunomodulating conditions in different compartments of the murine upper and lower respiratory tract (URT&LRT).MethodsPigr gene expression in lung, trachea, and nasal-associated lymphoid tissue (NALT) of germ-free mice, specific pathogen-free mice, mice with an undefined microbiome, as well as LPS- and IFN-γ-treated mice was determined by quantitative real-time PCR. IgA levels in bronchoalveolar lavage (BAL), nasal lavage (NAL), and serum were determined by ELISA. LPS- and IFN-γ-treated mice were colonized with Streptococcus pneumoniae and bacterial CFUs were determined in URT and LRT.ResultsRespiratory Pigr expression and IgA levels were dependent on the degree of exposure to environmental microbial stimuli. While immunostimulation with LPS and IFN-γ differentially impacts respiratory Pigr expression and IgA in URT vs. LRT, only prophylactic IFN-γ treatment reduces nasal colonization with S. pneumoniae.ConclusionAirway-associated secretory immunity can be partly modulated by exposure to microbial ligands and proinflammatory stimuli. Prophylactic IFN-γ-treatment modestly improves antibacterial immunity in the URT, but this does not appear to be mediated by SIgA or pIgR.

KDP, a Lactobacilli Product from Kimchi, Enhances Mucosal Immunity by Increasing Secretory IgA in Mice and Exhibits Antimicrobial Activity.

The potential of KDP, a lactic acid bacterial strain of Lactobacillus sakei, to enhance the production of mucosal specific immunoglobulin A (IgA) in mice and thereby enhance gut mucosal immunity was examined. KDP is composed of dead cells isolated from the Korean traditional food kimchi. Female BALB/c mice orally received 0.25 mg KDP once daily for 5 weeks and were co-administrated ovalbumin (OVA) for negative control and cholera toxin for positive control. Mice administered KDP exhibited increased secretory IgA (sIgA) contents in the small intestine, Peyer’s patches, serum, colon, and lungs as examined by ELISA. KDP also significantly increased the gene expression of Bcl-6, IL-10, IL-12p40, IL-21, and STAT4. In addition, KDP acted as a potent antioxidant, as indicated by its significant inhibitory effects in the range of 16.5–59.4% for DPPH, nitric oxide, maximum total antioxidant capacity, and maximum reducing power. Finally, KDP exhibited potent antimicrobial activity as evidenced by a significant decrease in the growth of 7 samples of gram-negative and gram-positive bacteria and Candida albicans. KDP’s adjuvant effect is shown to be comparable to that of cholera toxin. We conclude that KDP can significantly enhance the intestine’s secretory immunity to OVA, as well as act as a potent antioxidant and antimicrobial agent. These results suggest that orally administered KDP should be studied in clinical trials for antigen-specific IgA production.

Pollen Diet-Properties and Impact on a Bee Colony.

Simple SummaryIn order to study the effects of malnutrition in bees, attention should be drawn to the dietary composition. A pollen diet plays an important role in the life of bees. A well-balanced diet influences the development of the larvae as well as the physiology, biochemistry, immunity and histology of the workers.Diet is an important factor in the proper development of the individual and the entire colony. A pollen diet affects honey bees in a number of ways. It can stimulate the number and type of hemocytes, the total number of proteins, carbohydrates and lipids, affect the histology of the middle intestine, and ensure the correct ontogenesis of the larvae. Moreover, selected single-flower diets can stimulate the development of the pharyngeal glands that produce royal jelly, thus conditioning the development of secretory immunity. Selected single-species pollen may also increase the phenol oxidase concentration, which contributes to the humoral response. A honey bee diet based on multi-flower pollen is more desirable than a mono-flower diet, but must be properly balanced.

Secretory immune status of oral cavity in the patients with <i>Сandida</i>-associated denture stomatitis

Age-related changes in the oral mucosa immunity, including decreased contents of secretory immunoglobulins and antimicrobial peptides in saliva, along with changed balance of pro- and antiinflammatory cytokines, care risks for development of purulent-inflammatory or allergic diseases of the oral cavity. For example, denture stomatitis (DS) caused by Candida albicans occurs in about 30—70% of denture users. The purpose of this study was to assess the secretory immune state of oral mucous membranes in the patients with Candida-associated denture stomatitis. We examined 42 elderly patients (61-72 years old) with one-piece acrylic dentures for at least, 6 months (15 men and 27 women). Based on clinical and microbiological studies, the patients were divided into a group with DS (n = 24) and a group without DS (n = 18). The contents of secretory immunoglobulin A (sIgA) and proinflammatory cytokines was determined, i.e., interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNFα), and anti-inflammatory cytokines, e.g., receptor antagonist of interleukin-1 (RAIL), interleukin-4 (IL-4), interleukin-10 (IL-10), as well as antimicrobial peptides (cathelicidin LL-37, lactoferrin and alphadefensins 1-3 (HNP1-3). The sIgA levels in the salivary fluid of patients with DS (0.92 (0.80-1.26) g/l) were significantly lower (p < 0.05) than in patients without stomatitis (1.71 (1.23-2,13) g/l). In the group with advanced DS, a significant increase of IL-1β levels in saliva was observed, along with simultaneous decrease of IL-8 concentrations, compared to the other group, without differences in TNFα and IL-6 concentrations. Increased contents of IL-10 in saliva was also noted. It was shown that the concentrations of cathelicidin LL-37 in saliva of the DS patients was increased two-fold, whereas the contents of neutrophil-derived alpha-defensins (HNP 1-3) was decreased. Conclusions: The development of inflammation in denture stomatitis caused by usage of removable acrylic dentures associated with Candida albicans infection is characterized by functional insufficiency of the secretory immunity of the oral mucosa associated with decreased amounts of secretory immunoglobulin A and antimicrobial peptides of neutrophilic origin. Low levels of alpha-defensins may suggest a decrease in the functional activity of neutrophils in the elderly, thus leading to higher susceptibility to fungal infection of oral cavity.

Effect of Peptide Bioregulation on the State of Secretory Immunity in the Saliva of Elderly Patients with Chronic Generalized Periodontitis

Effect of Peptide Bioregulation on the State of Secretory Immunity in the Saliva of Elderly Patients with Chronic Generalized Periodontitis

Toll like receptors agonists-based nanomedicines as veterinary immunotherapies

<img src=” https://s3.amazonaws.com/production.scholastica/article/13493/large/prnano_482020_ga.jpg?1593185863”> Many infections affecting animals enter across mucosa, needing of secretory immunity to reject the disease; protection against some pathogens must be early, fast, and specifically elicited, while from others must be wide enough to fight against variable serotypes. Today, however, most veterinary vaccines are injectable (not recommended for chicken and small fishes), aimed to control clinical signs instead of eradicating the disease and poor inducers of secretory immunity. These drawbacks are compensated by vaccination with live attenuated agents, by using potentially toxic oily adjuvants and with indiscriminate use of antibiotics. In this review, the benefits of commercial and experimental nanomedicines acting as immunostimulants and vaccine adjuvants made of toll-like receptor (TLR) agonists loaded in nanoparticles (NP-TLR agonists), are presented. NP-TLR agonists induce a magnified, site-limited triggering of innate immunity; also allow modifying the administration route from injectable to mucosal or nebulized, provide structural protection to TLR agonists and avoid their diffusion far from the administration site. Future implementation of immunotherapies based on NP-TLR agonists will be discussed as a function of scale production feasibility.

Characterization of the complete genome sequence of the recombinant norovirus GII.P16/GII.4_Sydney_2012 revealed in Russia.

Noroviruses (the Caliciviridae family) are a common cause of acute gastroenteritis in all age groups. These small non-envelope viruses with a single-stranded (+)RNA genome are characterized by high genetic variability. Continuous changes in the genetic diversity of co-circulating noroviruses and the emergence of new recombinant variants are observed worldwide. Recently, new recombinant noroviruses with a novel GII.P16 polymerase associated with different capsid proteins VP1 were reported. As a part of the surveillance study of sporadic cases of acute gastroenteritis in Novosibirsk, a total of 46 clinical samples from children with diarrhea were screened in 2016. Norovirus was detected in six samples from hospitalized children by RT-PCR. The identified noroviruses were classified as recombinant variants GII.P21/GII.3, GII. Pe/GII.4_Sydney_2012, and GII.P16/GII.4_Sydney_2012 by sequencing of the ORF1/ORF2 junction. In Novosibirsk, the first appearance of the new recombinant genotype GII.P16/ GII.4_Sydney_2012 was recorded in spring 2016. Before this study, only four complete genome sequences of the Russian GII.P16/GII.3 norovirus strains were available in the GenBank database. In this work, the complete genome sequence of the Russian strain Hu/GII.P16-GII.4/RUS/Novosibirsk/NS16-C38/2016 (GenBank KY210980) was determined. A comparison of the nucleotide and the deduced amino acid sequences showed a high homology of the Russian strain with GII.P16/GII.4_Sydney_2012 strains from other parts of the world. A comparative analysis showed that several unique substitutions occurred in the GII.P16 polymerase, N-terminal p48 protein, and minor capsid protein VP2 genes, while no unique changes in the capsid VP1 gene were observed. A functional significance of these changes suggests that a wide distribution of the strains with the novel GII.P16 polymerase may be associated both with several amino acid substitutions in the polymerase active center and with the insertion of glutamic acid or glycine in an N-terminal p48 protein that blocks the secretory immunity of intestinal epithelial cells. Further monitoring of genotypes will allow determining the distribution of norovirus recombinants with the polymerase GII.P16 in Russia.

Could regular practice of volleyball modulate salivary secretory immunity in children? Cross-sectional and longitudinal studies

Introduction The aim of these studies was to evaluate the effects of regular volleyball training on salivary SIgA and alpha-amylase in female children and adolescents. Material and method In the cross-sectional study, 115 female children (12.6±2.2 years) participating in a Volleyball training program were classified as beginners, intermediate, and competitive level. The children were evaluated regarding caries index, body mass index (BMI), cardiorespiratory fitness, and countermovement jump. In the longitudinal study: 54 girls (intermediate and competitive groups) trained for 8 weeks and were re-evaluated at weeks 4 and 8. Results The SIgA secretion rate and alpha-amylase activity did not present correlations with training category, age, caries index, or training status. A weak positive correlation was detected between IgA secretion rate and BMI (r=0.20, p<0.05). After 8 weeks of training, VO2max (p<0.005) and jump height (p<0.005) improved in the competitive girls. No differences were observed in salivary secretion rate, SIgA concentration and secretion rate, or alpha-amylase activity at weeks 4 and 8. Conclusion We concluded that despite improving physical fitness, 8-weeks of recreational volleyball training are not able to improve salivary SIgA secretion or alter alpha-amylase activity in female children and adolescents.

Клінічні, імунологічні та метаболічні особливості загостреного і швидко прогресуючого варіантів генералізованого пародонтита

Summary. Generalized periodontitis is one of the most common and complex problems of modern dentistry. According to the WHO, its incidence corrects with age: in the group of individuals from 35 to 44 years, the prevalence of this pathology reaches more than 50 %, in people older than 65–78%, which leads to tooth loss in 40 % of cases. The complexity of the problem lies in the fact that generalized periodontitis is a multifactorial disease, which is characterized by a chronic course with a periodic exacerbation of the inflammatory process in periodontal disease. The progression of destructive phenomena in periodontal tissues depends on many reasons, the role of which from the moment of description and to this day remains the subject of debate and debate. The aim of this study is to assess the pathogenetic significance of disorders of the local components of the immune system, cytokine profile, processes of radical and antioxidant status, and features of bone remodeling in patients with aggressive generalized periodontitis. The work is based on the results of comprehensive clinical and laboratory studies of 123 patients with different course of generalized periodontitis. The study used generally accepted clinical, paraclinical and laboratory research methods, supplemented by dental volumetric tomography. The subjects were divided into 2 groups: I – with an aggravated course (62 people), II – with an aggressive (rapidly progressing) course of the disease (61 people), the control group consisted of 20 healthy volunteers. Studies have shown that exacerbated and rapidly progressing chronic generalized periodontitis is manifested by the same type of clinical symptoms and the same state of gingival and periodontal indices. In individuals with a high rate of destruction of periodontal bone structures, the activity of the inflammatory-destructive process and the rate of loss of periodontal bone tissue are caused by functional disorders of varying strengths: the state of local secretory immunity, the processes of free radical oxidation and the antioxidant defense system, changes in the cytokine profile, and is also found bone remodeling dysfunction due to increased processes of bone resorption and decreased bone formation. The need is substantiated, along with anamnestic data, to take into account the degree of increase in the levels of proinflammatory cytokines IL-1β and TNF-α, as well as features of bone metabolism and osteoparotic processes detected using dental volumetric tomography.