Foreign Pathogens Research Articles

PH-Responsive Mucus-Penetrating Nanoparticles for Enhanced Cellular Internalization by Local Administration in Vaginal Tissue.

Low mucus penetration ability and cellular uptake seriously limit the effectiveness of local vaginal drug administration because of the rapid foreign particulate and pathogen removal property of the mucus layer. Our previous work proved that nanoparticles with a highly dense polyethylene glycol (PEG) coating can penetrate mucus rapidly (mucus-penetrating nanoparticles, MPPs) and improve drug distribution and retention at mucosal surfaces. However, the "stealth-effect" of the PEG coating also restricts cellular uptake of MPPs. In this work, we designed pH-responsive mucus-penetrating nanoparticles (pMPPs) with hydrazone bonds as the linker to conjugate a dense PEG surface coating, which enabled the pMPPs to rapidly penetrate through the mucus layer. More importantly, the acidic environment of the vaginal mucus induces slow shedding of the PEG layer, leading to a positive charge exposure to facilitate cellular uptake. Overall, pMPPs demonstrate potential as an effective delivery platform for the prophylactic and therapeutic treatment of female reproductive diseases.

CAR T-Cell Therapy: Current Progress, Challenges and potential Strategies

In recent years, the unexpected development of immune system resistance in cancer cells has initiated development for new drug therapies that combat resistant cancer cells. One important issue is the mutation of antigens, which are able to help the cancer cells avoid immune system detection. As a result, the development of effective new therapies free from these problems is still a heavy focus in the medical community. Chimeric Antigen Receptor T-cells therapy is a new potential treatment that uses the infusion of genetically engineered immune system T-cells to recognize specific threats with the help of artificial T-cell receptors. Through extracting and engineering the blood sample of patients, foreign pathogens and cancer cells that aren’t yet able to be identified by the immune system can be recognized and detected by the CAR T-cells. This review paper aims to examine CAR T-cell treatments against ALL, focusing on the target antigens used in CAR design, variations in CAR generations, clinical trials and FDA approvals for CAR T-cells, obstacles in CAR T-cell treatments, and the best ways to overcome them.

PPARα alleviates inflammation via inhibiting NF-κB/Rel pathway in Vibrio splendidus challenged Apostichopus japonicus

Organisms trigger pro-inflammatory responses to resist the invasion of foreign pathogens in the early infection stage. However, excessive or chronic inflammation can also cause several diseases. We previously validated IL-17 from sea cucumbers mediated inflammatory response by the IL-17R-TRAF6 axis. But the anti-inflammatory effect was largely unknown in the species. In this study, the conserved PPARα gene was obtained from Apostichopus japonicus by RNA-seq and RACE approaches. The expression of AjPPARα was found to be significantly induced at the late stage of infection not only in Vibrio splendidus-challenged sea cucumbers, but also in LPS-exposed coelomocytes, which was negative correlation to that of AjIL-17 and AjNLRP3. Both silencing AjPPARα by specific siRNA and treatment with AjPAPRα inhibitor MK-886 could significantly upregulate the transcriptional levels of pro-inflammatory factors the AjIL-17 and AjNLRP3. The infiltration of inflammatory cells and tissues damage were also detected in the body walls in the same condition. In contrast, AjPAPRα agonist of WY14643 treatment could alleviate the V. splendidus-induced tissue injury. To further explore the molecular mechanism of AjPPARα-mediated anti-inflammatory in A. japonicus, the expression of the transcriptional factors of AjStat5 and AjRel (subunit of NF-κB) were investigated under AjPPARα aberrant expression conditions and found that AjRel exhibited a negative regulatory relationship to AjPPARα. Furthermore, silencing AjRel was led to down-regulation of AjIL-17 and AjNLRP3. Taken together, our results supported that AjPPARα exerted anti-inflammatory effects through inhibiting AjRel in response to V. splendidus infection.

DNA methyltransferase inhibition induces dynamic gene expression changes in lung CD4+ T cells of neonatal mice with E. coli pneumonia

Bacterial pulmonary infections are a major cause of morbidity and mortality in neonates, with less severity in older children. Previous studies demonstrated that the DNA of CD4+ T cells in the mouse lung, whose primary responsibility is to coordinate the immune response to foreign pathogens, is differentially methylated in neonates compared with juveniles. Nevertheless, the effect of this differential DNA methylation on CD4+ T cell gene expression and response to infection remains unclear. Here we treated E. coli-infected neonatal (4-day-old) and juvenile (13-day-old) mice with decitabine (DAC), a DNA methyltransferase inhibitor with broad-spectrum DNA demethylating activity, and performed simultaneous genome-wide DNA methylation and transcriptional profiling on lung CD4+ T cells. We show that juvenile and neonatal mice experienced differential demethylation in response to DAC treatment, with larger methylation differences observed in neonates. By cross-filtering differentially expressed genes between juveniles and neonates with those sites that were demethylated in neonates, we find that interferon-responsive genes such as Ifit1 are the most down-regulated methylation-sensitive genes in neonatal mice. DAC treatment shifted neonatal lung CD4+ T cells toward a gene expression program similar to that of juveniles. Following lung infection with E. coli, lung CD4+ T cells in neonatal mice exhibit epigenetic repression of important host defense pathways, which are activated by inhibition of DNA methyltransferase activity to resemble a more mature profile.

Expert consensus on the application of pathogenic diagnostic techniques for viral encephalitis and meningitis

Viral encephalitis (meningitis) is a common infectious disease of the central nervous system (CNS), which is an inflammatory disease caused by viruses invading the brain parenchyma and meninges. It is a global disease and a serious threat to human health as an acute and severe medical condition. CNS infections can be caused by a variety of viruses, including herpes viruses, enteroviruses, and arboviruses, etc. Identification and diagnosis of the pathogens remains a major clinical challenge. In order to standardize the application of nucleic acid and antibody tests of patients with viral encephalitis (meningitis), experts in the field of virology, infectious diseases, clinical medicine and laboratory testing in China reached the consensus after repeated discussions. The current consensus mainly consists of the domestic and foreign pathogen types, the detection techniques, the detection strategies and schemes for Chinese viral encephalitis, thereby providing a reference for the clinical diagnosis and disease prevention and control of viral encephalitis (meningitis).

Proteomics profiles reveal the potential roles of proteins involved in chicken macrophages stimulated by Lipopolysaccharide.

Lipopolysaccharide (LPS), a core part of gram-negative bacteria, is crucial for inducing an inflammatory response in living things. In the current study, we used LPS from Salmonella to stimulate chicken macrophages (HD11). Proteomics was used to investigate immune-related proteins and their roles further. Proteomics investigation revealed 31 differential expression proteins (DEPs) after 4 hours of LPS infection. 24 DEPs expressions were up-regulated, while seven were down-regulated. In this investigation, ten DEPs were mainly enriched in S. aureus infection, complement, and coagulation cascades, which were all implicated in the inflammatory response and clearance of foreign pathogens. Notably, complement C3 was shown to be up-regulated in all immune-related pathways, indicating that it is a potential protein in this study. This work contributes to a better understanding and clarification of the processes of Salmonella infection in chickens. It might bring up new possibilities for treating and breeding Salmonella-infected chickens.

NKG2D signaling shifts the balance of CD8 T cells from single cytokine- to polycytokine-producing effector cells.

CD8 T cells play a critical role in immunity against intracellular pathogens and cancer. A primary objective of T cell-based vaccine strategies is the induction of durable and effective immune responses. Achieving this goal involves more than simply boosting the numbers of responding T cells. Of particular interest is the induction of CD8 T cells with polycytokine capability, specifically with the ability of CD8 T cells to co-produce IFNγ, TNFα and IL-2. The presence of these polycytokine-producing CD8 T cells correlates strongly with protection against foreign pathogens and cancer. Therefore, approaches capable of inducing such polyfunctional responses are needed. NKG2D engagement on CD8 T cells has been shown to result in increased effector response. However, the manner in which NKG2D engagement results in improved CD8 T cell effector response is unclear. Here we demonstrate in vitro and in vivo that NKG2D engagement by its natural ligand, Rae-1ε, shifts the balance from single cytokine to polycytokine (IL-2, IFNγ, and TFNα) production. These data define a previously unrecognized process in which NKG2D costimulation on CD8 T cells results in improved effector responses.

B cell depletion therapies in autoimmune diseases: Monoclonal antibodies or chimeric antigen receptor-based therapy?

Immune system detects foreign pathogens, distinguishes them from self-antigens and responds to defend human body. When this self-tolerance is disrupted, the overactive immune system attacks healthy tissues or organs and the autoimmune diseases develop. B cells and plasma cells contribute a lot to pathogenesis and persistence of autoimmune diseases in both autoantibody-dependent and autoantibody-independent ways. Accumulating data indicates that treatments aiming to eliminate antibody-secreting cells (B cells or plasma cells) are effective in a wide spectrum of autoimmune diseases. Monoclonal antibodies (mAbs) deplete B cell lineage or plasma cells by signaling disruption, complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Engineered-T cells armed with chimeric antigen receptors (CARs) have been adopted from field of hematological malignancies as a method to eliminate B cells or plasma cells. In this review, we update our understanding of B cell depletion therapies in autoimmune diseases, review the mechanism, efficacy, safety and application of monoclonal antibodies and CAR-based immunotherapies, and discuss the strengths and weaknesses of these treatment options for patients.

Airway mucus in pulmonary diseases: Muco-adhesive and muco-penetrating particles to overcome the airway mucus barriers

Airway mucus is a complex viscoelastic gel that provides a defensive physical barrier and shields the airway epithelium by trapping inhaled foreign pathogens and facilitating their removal via mucociliary clearance (MCC). In patients with respiratory diseases, such as chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), non-CF bronchiectasis, and asthma, an increase in crosslinking and physical entanglement of mucin polymers as well as mucus dehydration often alters and typically reduces mucus mesh network pore size, which reduces neutrophil migration, decreases pathogen capture, sustains bacterial infection, and accelerates lung function decline. Conventional aerosol particles containing hydrophobic drugs are rapidly captured and removed by MCC. Therefore, it is critical to design aerosol delivery systems with the appropriate size and surface chemistry that can improve drug retention and absorption with the goal of increased efficacy. Biodegradable muco-adhesive particles (MAPs) and muco-penetrating particles (MPPs) have been engineered to achieve effective pulmonary delivery and extend drug residence time in the lungs. MAPs can be used to target mucus as they get trapped in airway mucus by steric obstruction and/or adhesion. MPPs avoid muco-adhesion and are designed to have a particle size smaller than the mucus network, enhancing lung retention of particles as well as transport to the respiratory epithelial layer and drug absorption. In this review, we aim to provide insight into the composition of airway mucus, rheological characteristics of airway mucus in healthy and diseased subjects, the most recent techniques to study the flow dynamics and particle diffusion in airway mucus (in particular, multiple particle tracking, MPT), and the advancements in engineering MPPs that have contributed to improved airway mucus penetration, lung distribution, and retention.

Cera-Glow, ferment lysates of Lacticaseibacillus rhamnosus IDCC 3201, improves skin barrier function in clinical study.

Ceramides are essential lipids in stratum corneum for skin permeability barrier function in that they retain the skin moisture and protect from the invasion of foreign pathogens. Previously, we demonstrated that ferment lysates of Lacticaseibacillus rhamnosus IDCC 3201 enhanced ceramide production in human epidermal keratinocytes. Furthermore, for comprehensive knowledge of this effect, in vitro experiments and multi-omics analysis were conducted to explore the underlying mechanisms. This study was designed to identify whether a cosmetic sample (i.e., Cera-Glow) containing the lysates improves the skin barrier function in clinical trials. Twenty-four female participants (45.46 ± 9.78 years) had been enrolled in the transepidermal water loss (TEWL) measurement for 5 days and 21 female participants (50.33 ± 5.74 years) had undergone a skin hydration evaluation for 4 weeks. TEWL and skin hydration were evaluated using a Tewameter and the Epsilon Permittivity Imaging System, respectively. After applying the Cera-Glow sample, all participants recorded a satisfaction survey questionnaire (e.g., satisfaction, efficacy, and adverse reactions). Application of Cera-Glow significantly improved transepidermal water loss induced by 1% (w/v) sodium lauryl sulfate (p < 0.05-0.01) and increased skin hydration (p < 0.01). Metabolic analysis suggested that Cera-Glow should contain beneficial gradients for skin barrier function. According to the questionnaire, most of participants were satisfied with the skin hydration improvement and efficacy of Cera-Glow. Cera-Glow, ferment lysates of Lacticaseibacillus rhamnosus IDCC 3201, can significantly improve skin barrier function.

Quantifying changes in the T cell receptor repertoire during thymic development.

One of the feats of adaptive immunity is its ability to recognize foreign pathogens while sparing the self. During maturation in the thymus, T cells are selected through the binding properties of their antigen-specific T-cell receptor (TCR), through the elimination of both weakly (positive selection) and strongly (negative selection) self-reactive receptors. However, the impact of thymic selection on the TCR repertoire is poorly understood. Here, we use transgenic Nur77-mice expressing a T-cell activation reporter to study the repertoires of thymic T cells at various stages of their development, including cells that do not pass selection. We combine high-throughput repertoire sequencing with statistical inference techniques to characterize the selection of the TCR in these distinct subsets. We find small but significant differences in the TCR repertoire parameters between the maturation stages, which recapitulate known differentiation pathways leading to the CD4+ and CD8+ subtypes. These differences can be simulated by simple models of selection acting linearly on the sequence features. We find no evidence of specific sequences or sequence motifs or features that are suppressed by negative selection. These results favour a collective or statistical model for T-cell self non-self discrimination, where negative selection biases the repertoire away from self recognition, rather than ensuring lack of self-reactivity at the single-cell level.

Molecular characterization of two newly identified glycine rich crustin genes (Mn-Gly-Cru3, Mn-Gly-Cru4) and their function in Macrobrachium nipponense innate immunity

Crustin, as an important antibacterial peptide in crustacean, plays a role in the defense against the invasion of foreign pathogens in the innate immune system. In this study, two glycine rich crustin genes (named as Mn-Gly-Cru3 and Mn-Gly-Cru4) were cloned in Macrobrachium nipponense. The full-length cDNA of Mn-Gly-Cru3 and Mn-Gly-Cru4 were 740 and 781 bp with open reading frames of 525 and 576 bp that encode 174 and 191 amino acids, respectively. The genome structure of Mn-Gly-Cru3 and Mn-Gly-Cru4 shows that both contain two exons and one intron. Both Mn-Gly-Cru3 and Mn-Gly-Cru4 protein contains a signal peptide, a cysteine-rich region, a glycine-rich region, and a whey acidic protein domain. Evolutionary analysis showed that Mn-Gly-Cru1, Mn-Gly-Cru2, Mn-Gly-Cru3 and Mn-Gly-Cru4 were clustered together. Mn-Gly-Cru3 and Mn-Gly-Cru4 were widely distributed in multiple tissues. After white spot syndrome virus (WSSV), Staphylococcus aureus or Vibrio parahaemolyticus challenge, the expression levels of Mn-Gly-Cru3 and Mn-Gly-Cru4 in the hemocytes, gills, and stomach were significantly changed. Mn-Gly-Cru3 and Mn-Gly-Cru4 knockdown remarkably increased the copy number of WSSV and the number of S. aureus and V. parahaemolyticus colonies in vivo. Purified rMn-Gly-Cru3 and rMn-Gly-Cru4 proteins could bind to a variety of bacteria and they also had binding activity toward LPS or PGN. Furthermore, rMn-Gly-Cru4 had a stronger binding activity to polysaccharides than rMn-Gly-Cru3. Our study indicates that Mn-Gly-Cru3 and Mn-Gly-Cru4 in M. nipponense are involved in the innate immune defense against bacteria or viruses.

COVID-19 (Symptomatic Non-Respiratory) with Type 2 Diabetes Mellitus

COVID-19 is a respiratory infection caused by a new strain of Coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which is highly contagious, primarily through respiratory droplets and contact. Typical symptoms include fever, cough, and shortness of breath. Weakness, nausea, and vomiting are often accompanied by respiratory symptoms but are sometimes confusing when these symptoms occur without respiratory symptoms. COVID-19 can affect any age group, are more common in adults and males and increase in patients with comorbidities. One of the most common comorbidities is Diabetes Mellitus (DM). A 40-year-old male patient complained of fever and weakness for three days. Nausea and vomiting since nine days before hospital admission, accompanied by painful swallowing, heartburn, and decreased appetite. History of going out of town and eating with friends 14 days before access to the hospital. 3 3 Laboratory examination results: 6600 leukocytes/mm , 264,000/mm platelets, NLR 2.3, 209 mg/dL of blood glucose, HbA1C 8.6%, SGOT 67 IU/L, SGPT 102 IU/L, IgG SARS-CoV-2 reactive, positive TCM SARS-CoV-2 (N2 Ct 18 and E Ct 20.3), and the duration of negative conversion of RT-PCR SARS-CoV-2 results was 19 days. The SARS-CoV-2 virus not only infects pneumocytes but also gastrointestinal, pancreatic, and endothelial cells via ACE2 receptors in DM patients, causing increased cell wall permeability to foreign pathogens and viral replication in the gastrointestinal lining cells. Subsequent enterocyte invasion causes malabsorption resulting in enteric symptoms. Uncontrolled glycemia conditions can slow viral shedding, so the length of negative conversion of RT-PCR SARS-CoV-2 results is prolonged. Based on the data above, the diagnosis in this patient was COVID-19 (symptomatic non-respiratory) with type 2 DM.

Design, Characterization, and Biological Activities of Erythromycin-Loaded Nanodroplets to Counteract Infected Chronic Wounds Due to Streptococcus pyogenes.

Streptococcus pyogenes causes a wide spectrum of diseases varying from mild to life threatening, despite antibiotic treatment. Nanoparticle application could facilitate the foreign pathogen fight by increasing the antimicrobial effectiveness and reducing their adverse effects. Here, we designed and produced erythromycin-loaded chitosan nanodroplets (Ery-NDs), both oxygen-free and oxygen-loaded. All ND formulations were characterized for physico-chemical parameters, drug release kinetics, and tested for biocompatibility with human keratinocytes and for their antibacterial properties or interactions with S. pyogenes. All tested NDs possessed spherical shape, small average diameter, and positive Z potential. A prolonged Ery release kinetic from Ery-NDs was demonstrated, as well as a favorable biocompatibility on human keratinocytes. Confocal microscopy images showed ND uptake and internalization by S. pyogenes starting from 3 h of incubation up to 24 h. According to cell counts, NDs displayed long-term antimicrobial efficacy against streptococci significantly counteracting their proliferation up to 24 h, thanks to the known chitosan antimicrobial properties. Intriguingly, Ery-NDs were generally more effective (104-103 log10 CFU/mL), than free-erythromycin (105 log10 CFU/mL), in the direct killing of streptococci, probably due to Ery-NDs adsorption by bacteria and prolonged release kinetics of erythromycin inside S. pyogenes cells. Based on these findings, NDs and proper Ery-NDs appear to be the most promising and skin-friendly approaches for the topical treatment of streptococcal skin infections allowing wound healing during hypoxia.

Assessment of Mound Soils Bacterial Community of the Red Imported Fire Ant, Solenopsis invicta across Guangdong Province of China

Soil microbes have a wide range of distribution across the world and can be found in different agricultural and forest systems including cultivated soils, ant mounds, decaying trees, leaves, roots, and on insect bodies. Across five counties of Guangdong province of China, the assemblage of bacterial associates of red imported fire ant (RIFA) were examined. The locations were selected based on evidence of high presence of RIFA mounds in these regions. Samples were analyzed from mound soils, plant debris within mounds, and the ant body. The current study analyzed bacterial species composition and richness patterns, where 525 isolates were recovered in total, comprising 44 bacterial taxa. Taxa abundance was highest in the ant body at 35 taxa, while the values were relatively similar across soil substrate and plant debris, where 3 and 6 taxa, respectively, were recorded. The highest bacterial taxa recovery rate was recorded in Guangzhou, where a total of 17 taxa were isolated. Myroides odoratimimus was the most common across all substrates and locations among the bacterial taxa. Others with the highest isolation frequencies includes, Enterobacter cloacae, Vagococcus fluvialis, and Myroides odoratus. The understanding of the bacterial community composition of RIFA is crucial for the development of successful management techniques for these notorious social ants. In order to expand on the findings of the current study, it is imperative to understand if the associated microbial communities of the RIFA form a parasitic, antagonistic, or mutualistic relationship with their host. In this vein, further studies would examine the influence of the characterized bacterial associates of the RIFA on the social behavior, physiology, and the host response to foreign pathogens.

Fibrosis in Liver and Pancreas: a Review on Pathogenic Significance, Diagnostic Options, and Current Management Strategies.

Inflammation is one of the most natural ways of the body's biological response against invading foreign pathogens or injured cells which eventually can lead to a chronic or acute productive response. Fibrosis is an end-stage event associated with an inflammatory response addressed with tissue hardening, discoloration, and most importantly overgrowth of associated tissue. Various organs at different diseased conditions are affected by fibrosis including the liver, pancreas, brain, kidney, and lung. Etiological factors including internal like inflammatory cytokines, growth factors, and oxidative stress and external like alcohol and viruses contribute to the development of fibrosis in both the liver and pancreas. More frequently, these organs are associated with pathogenic progression towards fibrosis from acute and chronic conditions and eventually fail in their functions. The pathogenesis of the organ-fibrotic events mainly depends on the activation of residential stellate cells; these cells help to accumulate collagen in respective organs. Various diagnostic options have been developed recently, and various therapeutic options are in trial to tackle fibrosis. In this review, an overview on fibrosis, the pathogenesis of fibrosis in the liver and pancreas, various diagnostic options developed in recent years, and possible present therapeutic measures to overcome options of fibrosis in the liver and pancreas; thus, restoring the functional status of organs is discussed.

Razlike biohemijskih, hematoloških i koagulacionih parametara među pacijentima sa blagom i teškim oblicima COVID-19

Introduction: Covid-19 is an infectious disease caused by the severe acute respiratory syndrom coronavirus 2 and causes a series of respiratory symptoms. Considering the appearance and development of symptoms, the course of Covid-19 can go from mild to severe. Depending on the course of Covid-19, the laboratory parameters change a lot, trying to defend the organism against the foreign pathogen and all the changes it causes. Therefore, the aim of this study is to observe the differences between biochemical, hematological and coagulation parameters depending on the disease stage of Covid-19 patients. Material and methods: We conducted cross-sectional study which included 160 Covid-19 patients from Sarajevo, Bosnia and Herzegovina. Biochemical, hematological and coagulation analyzes were performed. Results: Covid-19 patients with a severe clinical course have higher average values of fibrinogen (6.53 ± 4.47, p &lt; 0.001), D-dimer (6.89 ± 7.81, p &lt; 0.001), APTT (32.05 ± 5.96, p = 0.002), eosinophil (0.66 ± 0.09, p = 0.002) and CRP (93.42 ± 75.86, p = 0.023), and lower values of lymphocytes (1.04 ± 0.98, p &lt; 0.001), monocytes (0.45 ± 0.3, p &lt; 0.001), compared to Covid-19 patients with a mild clinical course. Covid-19 patients with a severe clinical course had higher average values of neutrophils (10.12 ± 5.80, p = 0.002) and lower values of reactive lymphocytes (0.02 ± 0.03, p &lt; 0.001) compared to Covid-19 patients with a mild clinical course. Conclusion: Biochemical, hematological and coagulation parameters can be a sensitive and specific biomarker for distinction of mild and severe Covid-19.

The Role of Mononuclear Phagocytes in the Testes and Epididymis

The mononuclear phagocytic system (MPS) is the primary innate immune cell group in male reproductive tissues, maintaining the balance of pro-inflammatory and immune tolerance. This article aims to outline the role of mononuclear macrophages in the immune balance of the testes and epididymis, and to understand the inner immune regulation mechanism. A review of pertinent publications was performed using the PubMed and Google Scholar databases on all articles published prior to January 2021. Search terms were based on the following keywords: 'MPS', 'mononuclear phagocytes', 'testes', 'epididymis', 'macrophage', 'Mφ', 'dendritic cell', 'DC', 'TLR', 'immune', 'inflammation', and 'polarization'. Additionally, reference lists of primary and review articles were reviewed for other publications of relevance. This review concluded that MPS exhibits a precise balance in the male reproductive system. In the testes, MPS cells are mainly suppressed subtypes (M2 and cDC2) under physiological conditions, which maintain the local immune tolerance. Under pathological conditions, MPS cells will transform into M1 and cDC1, producing various cytokines, and will activate T cell specific immunity as defense to foreign pathogens or self-antigens. In the epididymis, MPS cells vary in the different segments, which express immune tolerance in the caput and pro-inflammatory condition in the cauda. Collectively, MPS is the control point for maintaining the immune tolerance of the testes and epididymis as well as for eliminating pathogens.

St Sebastian

The image of St. Sebastian, as well as St. Edmund whom died in a similar vain, being shot with arrows though unharmed is well known. It raises a sense of unfeeling being a resultant of deliberate faith, though not in the hands of man but God. Nonetheless, in both saint’s cases it forms a clear act of resistance and defiance. In more recent interpretations by historians, the arrows shot into St. Sebastian have been interpreted as foreign pathogens attacking the body, medicalising the image, and reminding us of the harm experienced during the Covid pandemic, all caused by a non-anthropomorphic unconscious agent. Here, the arrows are bent and twisted, taking unfeeling as a deliberate response into humanity’s own hands. Drawing in pen.

VEGF gene polymorphism in complicated infective endocarditis

Introduction. Infective endocarditis (IE) is a bacterial disease with frequent pathogen localization on the heart valve apparatus. IE is characterized by rapid development of heart failure and frequent thromboembolic complications (TEC). IE features are accounted for by foreign pathogen nature and state of human immune system (IS). The imbalanced IS in infective endocarditis is manifested by impaired cytokine-mediated interactions. This confirms the rationality of studying cytokines to advance understanding of the pathogenesis for various conditions. Most cytokine genes are characterized by polymorphism and existing isoforms underlying disease predisposition. Genetic polymorphism of vascular endothelial growth factor A (VEGF-A) plays an important role in the induction of vasculogenesis and angiogenesis. The pathogenetic VEGF role in IE has not been thoroughly studied. Research objective analysis of polymorphic nucleotide sequence variants in the vascular endothelial growth factor gene, taking into account a relation with its serum concentration in patients with infective endocarditis. Materials and methods. 86 patients treated with verified diagnosis of infective endocarditis at the Scientific Research Institute Regional Clinical Hospital No. 1 of Krasnodar were divided into two clinical groups in accordance with the IE course: Group 1 IE with TEC (n = 44), group 2 IE without TEC (n = 42), and the control group consisted of 20 apparently healthy individuals. The concentration of serum VEGF-A (pg/mL) was measured by ELISA on day 1 of hospitalization. Genomic DNA was isolated from whole blood leukocytes and used to determine the frequency of genotypes of VEGF gene polymorphic variants. Results. Significant differences in the frequency distribution of VEGF-rs2010963 genotypes between patients with infective endocarditis and control group were revealed: G/G (OR = 0.25; p = 0.012) and G/C (OR = 4.28; p = 0.022), as well as differences between VEGF concentrations for various SNP-rs2010963 genotypes (p = 0.0001). A study of VEGF genotype frequency distribution between patients of clinical groups showed a significantly decreased frequency of the genotype G/G (rs2010963) in the IE group with TEC (OR = 0.21; p = 0.014) and increased frequency of G/C (OR = 4.72; p = 0.024) compared with the control group, whereas in patients with IE without TEC, significant (p = 0.0003) differences in serum concentrations of VEGF-rs2010963 were found in accordance with genotypes GG/CC (p = 0.01) and GG/GC (p = 0.003). Conclusion. The relationship between the VEGF genotypes (G/G and G/C of rs2010963 polymorphism) and related serum concentration among patients with IE was revealed. Carriers of the minor C allele (rs2010963) had higher serum VEGF levels. The results obtained complement and systematize current scientific data on the disease pathogenesis, as well as focus on the genetic determinant of the developing complications.