Archivum Immunologiae et Therapiae Experimentalis最新文献

Increased activity of B lymphocytes underpins many autoimmune conditions. A key component of the humoral immune response involves the A PRoliferation-Inducing Ligand (APRIL) and B-cell-activating factor (BAFF) system. These proteins are responsible for the activation, maturation, and survival of B lymphocytes, playing a pivotal role in autoimmunity. Therefore, targeting the BAFF/APRIL system proves promising for the treatment of various autoimmune diseases. Meticulous research into pathomechanisms of lupus nephritis (LN) has enabled the introduction of biological treatments targeting the BAFF-mediated pathway, significantly improving prognosis. In certain types of glomerulonephritis (GN), increased levels of the BAFF/APRIL system might be associated with higher proteinuria, elevated serum creatinine, but also with specific histopathological features. This indicates that biological therapies currently available could be repurposed for conditions where increased activation of B lymphocytes plays a critical role in the disease's pathophysiology. Understanding the mechanisms underlying autoimmune diseases will facilitate the adaptation of novel drugs for orphan diseases. That is why the use of chimeric antigen receptor T (CAR-T) cells as agents against B-cells receptor (BCR), represents a highly targeted and potentially optimal treatment approach. This study summarizes current knowledge about the role of the BAFF/APRIL system in lymphocyte activation mechanisms, particularly in GN. It also discusses existing biological treatments and explores future directions for drug development based on the CAR-T cell technology.

Diffuse large B-cell lymphoma (DLBC) is one of the usual forms found in indolent or invasive non-Hodgkin's lymphoma. Cancerous inhibitor of protein phosphatase 2A (CIP2A) has been revealed to be dysregulated in multiple cancers and is closely associated with tumor growth. However, the regulatory influences of CIP2A in DLBC progression remain unclear. The protein expressions were determined through western blot. Cell survival was assessed through the CCK-8 assay. Cell proliferation was examined through colony formation assay. The cell migration and invasion were inspected through transwell assay. First, it was discovered that CIP2A exhibited higher expression in DLBC. Additionally, inhibition of CIP2A restrained cell growth and metastasis in DLBC. Next, it was discovered that E-cadherin protein expression was ascended as well as N-cadherin and α-SMA protein expressions were descended after CIP2A knockdown, indicating that CIP2A suppression can retard the epithelial-mesenchymal transition (EMT) progress in DLBC. Finally, it was demonstrated that suppression of CIP2A retarded the Wnt/β-catenin pathway. It was manifested that high expression of CIP2A can aggrandize cell proliferation, migration, and EMT process in DLBC, and triggered the Wnt/β-catenin pathway. This finding implied that CIP2A may serve as a hopeful target for treating DLBC.

Although juvenile idiopathic arthritis (JIA) is the most common form of autoimmune-driven arthritis in pediatric population, due to the lack of universal diagnostic markers and heterogeneity of the disease, many patients face a significant delay when establishing the diagnosis. As the hallmark of JIA is the inflammation of synovial membrane with pathological angiogenesis, this study aimed to compare the concentrations of semaphorin 5A (SEMA5A), protein involved in both angiogenesis and immune response, between new-onset JIA and healthy controls. Thirty-five JIA patients and 35 sex-and-age matched healthy controls were enrolled in this study. Serum concentrations of SEMA5A and vascular endothelial growth factor A (VEGF-A) were established using the enzyme-linked immunosorbent assay (ELISA) method. The serum concentration of SEMA5A was elevated in JIA patients in comparison to healthy controls with the median value of 2.04 (interquartile range [IQR]: 12.41) in JIA patients and 1.34 (IQR: 1.79) in healthy controls (p = 0.002). The difference was particularly prominent in oligoarticular JIA, where median SEMA5A concentration equaled 1.76 ng/mL (IQR: 1.56) in comparison to 0.33 ng/mL (IQR: 1.34) in sex-and-age-matched healthy controls (p = 0.001). SEMA5A concentration correlated strongly with VEGF-A concentration (r = 0.807, p < 0.001) and differed significantly in subgroups of different synovial membrane power-Doppler ultrasound (PDUS) inflammatory activities (p = 0.018). Although our findings need to be repeated on larger groups of JIA patients, SEMA5A is a promising marker of JIA, linked to pathological angiogenesis of synovial membrane in this entity. Moreover, it may be useful as a target of innovative treatment strategies in the nearest future.

This study aimed to determine the efficacy of low molecular weight heparin (LMWH) and lidocaine combined with LMWH for improving the course of acute pancreatitis (AP). A total of 30 rats were divided into three groups: the NaCl group, which received an intraarterial infusion of 0.9% sodium chloride; the Heparin group, which received a subcutaneous injection of LMWH; and the Lidocaine-Heparin group, which received an intraarterial infusion of 1% lidocaine, with subsequent subcutaneous injection of LMWH. AP was triggered using 80 μg/kg body weight of cerulein. Serum amylase and lipase levels were evaluated before induction of AP (measurement 0 - M0), after triggering AP (measurement 1 - M1), 1 h (measurement 2 - M2), 3 h (measurement 3 - M3), and 5 h (measurement 4 - M4) after treatment. After euthanasia, pancreatic tissues were collected for pathological analysis. No intergroup differences in serum amylase and lipase levels were observed between the NaCl and Heparin groups in all post-treatment evaluation points (M2, M3, and M4). Conversely, the Lidocaine-Heparin group showed significantly lower amylase values than the NaCl and Heparin groups in all post-treatment evaluation points. Furthermore, the Lidocaine-Heparin group showed significantly lower lipase values compared with the NaCl group in the first post-treatment evaluation point (M2), as well as compared with the Heparin group in the first (M2) and second (M3) post-treatment evaluation points. No significant intergroup differences were observed in pathological pancreatic tissue evaluation. Subcutaneous injection of LMWH did not impact the natural course of AP. However, the addition of intraarterially administered 1% lidocaine solution significantly reduced the severity of AP.

Parkinson's disease (PD) affects millions of people globally. Accurate early diagnosis remains a challenge due to the lack of specific biomarkers. This systematic review explores the potential of ¹H-NMR metabolomics in identifying diagnostic markers and therapeutic targets for PD. A comprehensive analysis was conducted across databases such as Scopus, Web of Science, PubMed, and Embase, focusing on studies that utilized ¹H-NMR spectroscopy to profile metabolites associated with PD progression. The review identifies key metabolites-glutamate, taurine, myo-inositol, glutamine, and creatine-that play critical roles in the pathophysiology of PD. Glutamate, linked to excitotoxicity and neuronal degeneration, emerges as a prominent target for therapeutic intervention, while taurine is associated with oxidative stress. Myo-inositol, a key regulator of autophagy, underscores the biochemical dysregulation associated with PD, similar to glutamine and glutamate. Creatine's role in neuronal energy metabolism suggests potential avenues for treatment focused on energy supplementation. The reproducibility of metabolite findings varied, indicating the complexity of PD's metabolomic landscape. Despite challenges in consistency, these metabolites hold promise as biomarkers for diagnosing PD and tracking disease progression. The review underscores the need for further validation of these markers and their integration with other omics technologies to enhance PD management. By identifying key metabolic pathways, this study opens new directions for personalized medicine, offering potential therapeutic targets to slow disease progression and improve patient outcomes.

To investigate the effects of Sanguinarine (SAG) on the progression of diffuse large B-cell lymphoma (DLBCL) and to explore its underlying mechanism, this study utilized Epstein-Barr virus (EBV)-positive DLBCL cell lines, FARAGE, and GM12878S. Cell counting kit-8 and bromodeoxyuridine assays were used to assess the effects of SAG on the cell proliferation. Flow cytometry and immunoblotting were employed to analyze cell cycle arrest and apoptosis. Additionally, the molecular mechanism was explored through further immunoblotting analysis of the mechanism. SAG suppressed the growth of EBV-positive DLBCL cells. Furthermore, SAG induced cell cycle arrest and promoted apoptosis in these cells. Mechanistically, SAG suppressed the Wnt/β-catenin pathway, thereby suppressing DLBCL progression in vitro. SAG effectively inhibits cell growth and induces apoptosis in EBV-positive DLBCL via Wnt/β-catenin pathway, offering potential therapeutic insights for this lymphoma subtype.

Both disease and treatment carry the risk of thrombotic events in patients with rheumatoid arthritis (RA). This pilot study aimed to assess changes in thrombotic markers in plasma and their potential role as predictors of response during early baricitinib treatment. The concentrations of antithrombin III (ATIII) activity, D-dimer (DD), fibrinogen, and homocysteine (HCY) were evaluated in RA subjects before and 3 months after the treatment. At baseline, the RA group had higher DD (1472.3 ± 349.2) and fibrinogen (410.4 ± 29.5) compared with healthy controls (HC; 450.3 ± 54.5; p = 0.0002 and 334.9 ± 19.2; p = 0.04, respectively). with no differences in ATIII and HCY. After 3 months, we observed a significant increase in HCY (10.7 ± 0.6 vs. 9.1 ± 0.5; p = 0.018) and ATIII (119.7 ± 2.7 vs. 110.4 ± 3.2; p = 0.004), the latter correlated negatively with disease activity score 28 (DAS28; r = -0686, p < 0.002). After 3 months of baricitinib therapy, the patients were divided into moderate responders (MR) and good responders (GR) groups according to EULAR criteria. At baseline, MR had higher DD (1639.2 ± 550.5 vs. 450.3 ± 54.5; p < 0.0001) and lower ATIII (105.3 ± 3.6 vs. 115.1 ± 2.7; p = 0.043) compared with HC. Thrombotic parameters in the first 3 months of baricitinib treatment were mostly in line with current findings concerning the RA population. Increased levels of DD together with low ATIII concentrations seem to predispose to a moderate response to baricitinib treatment.

Nerve regeneration under unfavorable wound conditions remains challenging. We introduce the human epineural patch (hEP) as a novel nerve protector for post-trauma applications, comparing its regenerative efficacy with that of the human amniotic membrane (hAM). Following crush injury, transection, and end-to-end repair (CTR), 36 athymic nude rats were randomly assigned to six experimental groups (n = 6 each): control (no-protection), hEP, or hAM application post-repair. Assessments at 6 weeks and 12 weeks included functional evaluation (Toe-Spread and Pinprick tests), gastrocnemius muscle index (GMI), histomorphometric analysis (myelin thickness, axonal density, fiber diameter, percentage of myelinated fibers), and immunofluorescence staining for neurogenic, angiogenic, and immunogenic markers. The hEP group exhibited superior motor (3.167 ± 0.167) and sensory (3.500 ± 0.212) recovery and GMI values (0.955 ± 0.014), compared with the No protection group (p < 0.05). Myelin thickness (3.480 ± 0.019 µm, p < 0.0001), fiber diameter (10.788 ± 0.197 µm, p < 0.05), and myelinated fiber percentage (89.841% ± 0.453%, p < 0.01) were significantly higher in the hEP group. At 12 weeks, hEP application significantly increased the expression of Laminin B (2.083 ± 0.083), nerve growth factor (NGF) (1.750 ± 0.250), and vascular endothelial growth factor (VEGF) (2.667 ± 0.333), corresponding with improved function. The application of hEP at the sciatic nerve repair site after CTR injury significantly enhanced nerve regeneration compared with hAM. This study introduces hEP as a promising alternative nerve protector for traumatic nerve injuries.

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.