Archivum Immunologiae et Therapiae Experimentalis最新文献

Studies on the bacillus Calmette-Guérin (BCG) vaccine, traditionally used against tuberculosis, indicate its potential benefit in protecting against infections. The vaccine's ability to broadly activate the immune system suggests its potential to bolster non-specific immunity, which could be crucial for combating respiratory pathogens. This study aimed to evaluate the messenger RNA (mRNA) expression of interferon (IFN)-α, IFN-β, and IFN-γ as well as the secretion of these cytokines in whole blood co-stimulated cultures with BCG and antigens of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or respiratory syncytial virus (RSV) from BCG-vaccinated Polish children who have been infected or uninfected with RSV and/or SARS-CoV-2. Significant differences were observed in the secretion and mRNA expression of IFN-α and IFN-γ in response to RSV antigens in all groups of children studied. When cultures were conducted in the presence of SARS-CoV-2 antigens, live BCG did not induce increased IFN-α secretion compared with cultures stimulated with these antigens alone. However, enhanced secretion was observed for IFN-γ, and no such relationship was observed for mRNA expression. Furthermore, discrepancies between IFN-β secretion and mRNA expression were observed, suggesting that IFN protein secretion can also be controlled at the translational or posttranslational level. The data from our studies indicate that BCG vaccination may modulate the IFN response to viral challenges with SARS-CoV-2 and RSV, suggesting a potential immunoregulatory role.

Non-tuberculous mycobacteria (NTM) are increasingly recognized as opportunistic pathogens in humans and animals, particularly affecting those with compromised immune systems. These bacteria encompass a diverse group of mycobacterial species that are responsible for a range of infections, with pulmonary and skin-related conditions being the most common. The rise in NTM infections in recent years is a growing concern for healthcare, highlighting the urgent need to improve our understanding of NTM epidemiology and treatment strategies. This article reviews the NTM species associated with lung infections in immunocompromised patients and underscores the critical importance of advancing diagnostic and therapeutic approaches. The review is based on a thorough analysis of scientific literature from databases such as PubMed, Scopus, and ScienceDirect, covering studies up to June 2024. Through this comprehensive analysis, the article aims to provide detailed insights into the complexities of NTM diseases and spur further research and innovation in combating these challenging infections.

This study aims to investigate the effects and underlying mechanisms of isorhynchophylline (IRN) on gestational diabetes mellitus (GDM). The db/+ mice were randomly divided into four groups: GDM, GDM + IRN (20 mg/kg), and GDM + IRN (40 mg/kg). Blood glucose and insulin tolerance were assessed using intraperitoneal glucose tolerance tests (IPGTTs) and intraperitoneal insulin tolerance tests (IPITTs) on gestational day 10. On gestational day 20, placental inflammation (tumor necrosis factor [TNF]-α, interleukin [IL]-6, IL-1β), oxidative stress markers (malondialdehyde [MDA], SOD, glutathione peroxidase [GPx], and glutathione [GSH]), and nuclear factor-κB/NOD-like receptor protein 3 [NLRP3] inflammasome activity were measured using enzyme-linked immunosorbent assay (ELISA), immunoblotting, and biochemical assays. IRN significantly improved blood glucose levels and insulin tolerance in GDM mice. IRN treatment reduced placental inflammation. In addition, oxidative stress in the placenta was alleviated in the IRN-treated groups, leading to improved placental function and healthier fetal development. The birth weight of offspring was higher in the IRN-treated groups compared with untreated GDM mice. Furthermore, IRN inhibited the activation of the NLRP3 pathway. IRN significantly improves metabolic and inflammatory parameters in GDM through the NF-κB/NLRP3 pathway, highlighting its potential therapeutic benefits for managing GDM and improving maternal and fetal outcomes.

Antinuclear antibodies (ANAs) are critical immunological markers commonly associated with various connective tissue diseases (CTDs). However, these autoantibodies are also detectable in healthy individuals, patients with non-rheumatic autoimmune diseases, those with viral infections, and subjects using specific medications (such as procainamide, hydralazine, and minocycline) that can lead to drug-induced ANA elevation. The standard method for ANA detection is indirect immunofluorescence, a process that requires precision and thoroughness as it assesses both titer and fluorescence patterns. Additionally, immunoblotting and enzyme-linked immunosorbent assay (ELISA) are recommended to identify specific ANAs precisely, highlighting the importance of precision in ANA detection. This review explores the advantages and limitations of current ANA detection methods. It also describes the clinical implications of ANA presence in non-rheumatic diseases, including autoimmune disorders, infectious conditions, non-autoimmune and non-infectious diseases, and autoimmune cutaneous diseases. The presence of elevated ANA titers in these contexts can complicate clinical decision-making, as the diagnostic value of ANA testing alone is limited in non-rheumatic conditions. However, despite these limitations, ANA remains a key component in diagnosing and prognosis systemic CTDs, as it can indicate disease activity, severity, and response to treatment, which is of utmost importance in rheumatology and internal medicine. This paper provides a comprehensive review of the role of ANA in non-rheumatic diseases. It focuses on ANA diagnostic and prognostic significance and offers valuable insights for clinical practice.

Following its discovery as an adaptive immune system in prokaryotes, the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) system has been developed into a multifaceted genome editing tool. This review compiles findings aimed at implementation of this technology for selective elimination or attenuation of enterohemorrhagic Escherichia coli (EHEC). EHEC are important zoonotic foodborne pathogens that cause hemorrhagic colitis and can progress to the life-threatening hemolytic uremic syndrome (HUS). Advancements in the application of CRISPR methodology include laboratory detection and identification of EHEC, genotyping, screening for pathogenic potential, and engineering probiotics to reduce microbial shedding by cattle, the primary source of human infection. Genetically engineered phages or conjugative plasmids have been designed to target and inactivate genes whose products are critical for EHEC virulence.

Systemic lupus erythematosus (SLE) is an autoimmune disease whose pathogenesis is not fully understood to date. One of the suggested mechanisms for its development is NETosis, which involves the release of a specific network consisting of chromatin, proteins, and enzymes from neutrophils, stimulating the immune system. One of its markers is citrullinated histone H3 (H3Cit). This study aimed to evaluate the correlation of H3Cit levels with the clinical characteristics of 80 SLE patients. Levels of H3Cit in the subjects' serum were quantified spectrophotometrically. Statistical analysis was performed using MedCalc 15.8 and Statistica 13.3. Significantly higher H3Cit levels were found in patients with arthralgia (medians [interquartile range] [IQR]: 1.67 [1.67-1.69] vs. 1.67 [1.62-1.68], p = 0.0150, respectively) and reduced complement component C4 levels compared to patients without these conditions (medians [IQR]: 1.68 [1.67-1.70] vs. 1.68 [1.67-1.69], p = 0.0297, respectively). A significant weak negative correlation was observed between H3Cit levels and leukocytosis (rho = -0.2602, p = 0.0309) and reduced complement component C3 levels (rho = -0.2442, p = 0.0447) and a weak positive correlation with anti-double stranded DNA (anti-dsDNA) antibody levels (rho = 0.3794, p = 0.0036). Moreover, the clinical utility of the H3Cit assay in differentiating patients with arthralgia (area under the curve [AUC] = 0.709, p = 0.0115), seizures (AUC = 0.813, p = 0.0005), hepatomegaly (AUC = 0.746, p = 0.0111), and reduced levels of complement component C4 (AUC = 0.662, p = 0.0224) and without the above conditions was noted.

Hyperuricemia (HU) is a common disorder associated with gout, kidney injury, and high cardiovascular risk. However, whether high serum uric acid (sUA) is a causative factor or just comorbidity remains unclear. When asked if asymptomatic hyperuricemic patients need treatment, even artificial intelligence in the form of the GPT chat provides an ambivalent answer and refers us to a healthcare provider. We believe that such discrepancies stem from an incomplete understanding of the role that uric acid (UA) plays inside and outside the cell. With the rapid development of genomics, proteomics, immunology, and novel biomarkers, we are armed with new data to help us better understand the weight of inborn and environmental factors on an individual's UA concentrations. This review sums up the latest progress that has been made in the field of asymptomatic HU, compares the results presented by various research teams, and indicates new directions that emerge for future studies.

Vitamin D levels have been related to the severity and progression of various autoimmune disorders. In this study, we aimed to investigate the impact of genetic variability in the vitamin D receptor (VDR) gene on disease susceptibility and progression in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor (TNF) inhibitors. The study comprises 121 RA patients subjected to anti-TNF therapy genotyped for four VDR polymorphic variants: rs1544410 (BsmI), rs2228570 (FokI), rs731236 (TaqI), and rs7975232 (ApaI). There was no significant association between RA susceptibility and VDR genetic variants. The study results revealed that patients with the rs2228570 CC genotype were characterized by lower vitamin D3 levels (p = 0.028) than those with the T allele. Also, the vitamin D3 levels (p = 0.029) and age at diagnosis (p = 0.017) were significantly lower in rs7975232 A allele carriers compared to CC homozygotes. However, after 6 months of therapy, the A allele seemed to be related to lower disease activity score 28 (DAS28) values (p = 0.030) and more common in patients who achieved remission (p = 0.004) compared to the CC genotype. Concerning other investigated polymorphisms, patients carrying rs1544410 AA and rs731236 CC homozygosity had lower C-reactive protein (CRP) levels before therapy (p = 0.009). In conclusion, VDR rs2228570 and rs7975232 polymorphic variants were found to be related to vitamin D3 levels. Moreover, the genotyping of rs7975232 was also useful in evaluating disease onset and disease activity after 6 months of therapy with TNF inhibitors in RA patients.

AdoMet (S-adenosylmethionine) inhibits cancer cell proliferation and migration via epigenetic alterations. This study aimed to investigate whether AdoMet may cause alterations in microRNA (miRNA) expression profiles that are important for the initiation and progression of prostate cancer. PC-3 cells were treated with AdoMet before miRNA sequencing. A total of 17 differentially expressed miRNAs were detected. Target gene prediction was performed by means of databases. Results were aligned to transcriptomic data. The bioinformatic analysis revealed upregulation of anticancerogenic genes, downregulation of cancerogenic-related processes and pathways. Knocking down hsa-miR-192-5p in PC-3 cells resulted in downregulation of cancer cell proliferation, thus confirming these results.

Accumulating data have shown a pathophysiological association between inflammatory pathways and thrombosis. Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and acute pulmonary embolism (APE), is a significant health burden. It involves not only hemodynamic disturbances due to the emboli occluding the pulmonary arteries, but also platelet activation, endothelial dysfunction, and "firing up" of the inflammatory cascade. In humans, the systemic inflammatory state can also be evaluated using plasma levels of C-reactive protein (CRP) and interleukin (IL)-6, which correlate with venous obstruction, thrombus extension, and clinical VTE complications such as postthrombotic syndrome, recurrent thromboembolism, worse quality of life, and functional impairment. The exaggerated inflammatory state during postthrombotic syndrome aligns with severe alterations in endothelial function, such as activation of intercellular adhesion molecule (ICAM)-1 and E-selectin, as well as vascular proteolysis and fibrinolysis. Moreover, a hypercoagulable state, indicated by higher levels of von Willebrand factor (vWF) and factor VIII, is closely associated with the inflammatory response. We aimed to describe the role of basic inflammatory markers in daily clinical practice as well as the most important cytokines (IL-1β, IL-6, IL-8, tumor necrosis factor-a [TNF-α], growth differentiation factor-15 [GDF-15]). These markers could provide valuable insight into the interplay between thrombosis and inflammation, helping inform better management and treatment strategies.