Archivum Immunologiae et Therapiae Experimentalis最新文献

Neurodegenerative diseases, such as Parkinson's, Alzheimer's, and Huntington's, are major causes of disability. Current treatments are mostly symptomatic, due to a limited understanding of the disease mechanisms and the brain's poor regenerative capacity. Neuronal transdifferentiation offers a promising solution. Existing protocols are often inefficient, invasive, or time-consuming, and expensive. Furthermore, they mostly rely on nucleic acids as transdifferentiation-inducers, hence this carries risks of insertion mutagenesis. In this study, monocytes were isolated from buffy coats and cultured under four protocols using different small-molecule combinations. Two protocols successfully generated TUJ1⁺ MAP2⁺ SYP⁺ cells. Transdifferentiation is achievable through cheap and efficient chemical induction.

Antimicrobial peptides, which function as the first line of host immune defense, have recently been identified as important immunomodulators of inflammation, and are involved as regulatory molecules in infections, including sepsis. Treatment of sepsis is very complex and remains largely challenging and sometimes ineffective. This creates a need to develop new therapeutic strategies focusing not only on the elimination of sepsis-causing microorganisms, which can be achieved with antibiotics, but also on the control of the immune system and its overactive response resulting in increased vascular endothelial permeability. One approach to develop new treatments for patients with sepsis is to better understand the pleiotropic function of the human LL-37 peptide that originates from the human cathelicidin antibacterial protein (h-CAP18). An increasing number of studies indicate high dynamics of changes in LL-37 concentration in the blood during sepsis. Additionally, in animal models, administration of exogenous LL-37 peptide to mice with experimentally induced sepsis increases their survival. It can therefore be assumed that knowledge of the molecular mechanism of cathelicidin LL-37 action, as well as the synthesis of its stable analogs, will result in progress in the diagnosis and therapy of sepsis.

A narrative from a co-author of studies explaining the cellular mechanisms of self/nonself discrimination by the immune system, set against the backdrop of significant advancements in immunology during the last quarter of the 20th century. This review focuses on demonstrating the functional diversity of T cells by identifying their two major subsets: regulatory CD4 and cytotoxic CD8. It also examines the first T-cell receptor (TCR) transgenic mice, providing definitive evidence for both positive and negative selection of immature thymocytes as mechanisms for generating a self-tolerant and MHC-restricted TCR repertoire. The origins of these experiments have been discussed.

This study aimed to investigate the therapeutic potential of annexin A1 (ANXA1) overexpression in improving the signs of dry eye disease (DED) and to elucidate the underlying molecular mechanism. A murine model of DED was established by topical application of 0.2% benzalkonium chloride (BAC), and human corneal epithelial (HCE-T) cells were exposed to 0.0005% BAC for in vitro experiments. ANXA1 was overexpressed using adenoviral vectors, and the effects on tear production, pyroptosis, and activation of the tripartite motif-containing protein 72 (TRIM72)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway were evaluated using Western blotting, Schirmer test, Terminal deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) assays, and fluorescent probe analyses. To further examine the role of TRIM72, its expression was silenced with specific small interfering RNA (siRNA), and the consequent impact on ANXA1-mediated therapeutic effects was assessed. ANXA1 expression was significantly reduced in both in vivo and in vitro DED models. Restoration of ANXA1 through overexpression significantly improved tear secretion and suppressed pyroptosis in the murine model. Similarly, in HCE-T cells, ANXA1 overexpression not only enhanced cellular proliferation but also significantly inhibited pyroptosis. Mechanistic investigations demonstrated that ANXA1 overexpression activated the TRIM72/Nrf2/HO-1 signaling pathway by increasing TRIM72, Nrf2, and HO-1 expression. Notably, silencing TRIM72 abolished the therapeutic effects of ANXA1 overexpression, thereby confirming that activation of this pathway is essential for mediating the protective effects of ANXA1 against DED. Overexpression of ANXA1 inhibits pyroptosis and improves dry eye signs by regulating the TRIM72/Nrf2/HO-1 axis.

This study aims to investigate the role of MBD protein 2 (MBD2) in the pneumonia cell model of lipopolysaccharide (LPS)-stimulated WI-38 cells and to uncover the mechanism. LPS-stimulated WI-38 cells were constructed as an in vitro pneumonia model. Quantitative polymerase chain reaction (qPCR) and immunoblot assays showed MBD2 expression in WI-38 cells. Cell counting kit-8 (CCK-8) assays showed the growth of WI-38 cells. Flow cytometry assays showed the apoptosis of WI-38 cells after LPS treatment and siRNA transfection. Enzyme-linked immunosorbent assay (ELISA) and qPCR assays showed the effects on inflammation, and immunoblot assays further confirm the mechanism. MBD2 was highly expressed in LPS-stimulated WI-38 cells. Knockdown of MBD2 alleviates production of cellular inflammatory cytokines in LPS-stimulated WI-38 cells. Further, knockdown of MBD2 alleviates apoptosis in LPS-stimulated WI-38 cells. Mechanically, the knockdown of MBD2 regulates the signal transducer and activator of transcription (STAT)-3 pathway in LPS-stimulated WI-38 cells. Knockdown of MBD2 attenuates LPS-stimulated inflammation and apoptosis in WI-38 cells through the STAT-3 pathway. Therefore, MBD2 could serve as a promising target of pediatric pneumonia.

This study investigates the effects of intraoperative cell salvage (IOCS) on cell survival rates, apoptosis levels, and circulating tumor cell (CTC) counts in patients with hepatocellular carcinoma (HCC) undergoing curative resection. A combination of immunofluorescence, Western blot, flow cytometry, and qRT-PCR was employed to assess the impact of IOCS on cellular activity and CTC dynamics in these patients. No significant differences were found in demographic characteristics, including gender, age, body mass index (BMI), Child-Pugh classification, and liver function markers (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) between the experimental and control groups. Preoperatively, both groups exhibited low cell survival rates without statistical differences (P > 0.05), and cell survival remained similarly low during surgery. However, 6 h post-surgery, the experimental group showed a significant increase in cell survival rates compared with the control group (P < 0.05), suggesting that IOCS enhances postoperative cell viability. Apoptosis levels were similarly high in both groups before and during surgery (P > 0.05), but notably, 6 h post-operation, apoptosis levels in the experimental group were significantly reduced (P < 0.05), indicating effective prevention of cell death. Although preoperative CTC counts were low and increased during surgery, no significant differences were observed between groups during surgery. However, 6 h post-surgery, the experimental group exhibited a marked decrease in CTC counts (P < 0.05), indicating a reduction in tumor cell dissemination. Although these findings suggest that IOCS improves cell survival and reduces apoptosis and CTC counts, there is a potential concern regarding the possibility of IOCS preferentially preserving viable cells with metastatic potential. The long-term impact of this intervention on tumor recurrence or metastasis requires further investigation. In conclusion, IOCS appears to offer short-term benefits in enhancing postoperative cell survival and reducing CTC dissemination in patients with HCC; however, the potential risk of promoting metastatic cell viability warrants additional study before broader clinical application.

RING finger and WD repeat domain 3 (RFWD3) expression is elevated in various tumor types, but its precise role in non-small cell lung cancer (NSCLC) remains unclear. This study aims to investigate the biological function of RFWD3 in NSCLC and the associated molecular pathways. RFWD3 expression was knocked down in NSCLC cells through transfection. Cell apoptosis was analyzed using flow cytometry, cell viability was assessed using the cell counting kit-8 (CCK-8), and the migration and invasion of NSCLC cells were evaluated using Transwell chamber assays. Additionally, the expression of BAX, BCL-2, cleaved-caspase-3, and key signaling molecules involved in the ERK/p38 pathway was determined using Western blotting. The expression of RFWD3 was found to be elevated in NSCLC cells compared with normal lung epithelial BEAS-2B cells. Its knockdown led to reduced cell proliferation, migration, and invasion and increased apoptosis rate, partially through the inhibition of the ERK/p38 signaling pathway. Knockdown of the RFWD3 gene inhibited NSCLC cell proliferation, migration, and invasion while also inducing apoptosis. These effects are partially attributed to the blockade of the ERK/p38 signaling pathway.

IL-17RB is a cytokine receptor that binds interleukin (IL)-17B and IL-17E. While analyzing IL-17RB expression in various cancer cell lines, we found that this receptor is highly expressed at both the mRNA and protein levels in hepatocellular carcinoma (HCC) cells. This finding prompted us to investigate the effects of its ligand, IL-17B, on the proliferation of these cells. Our results demonstrate that IL-17B inhibits the proliferation of HCC cells through an AKT-dependent, but NF-κB-independent, mechanism. Additionally, IL-17B affected colony formation in these cells. Interestingly, these effects were not observed in melanoma cells, which express low levels of IL-17RB. Our results may represent a promising new approach for treating HCC - a disease for which immunological therapies have recently gained significant attention - especially considering that HCC patients experience progressive liver dysfunction and that the IL-17B-IL-17RB signaling pathway plays a role in liver regeneration.

This study aims to describe the impact of some of the most common autoimmune diseases, such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), myasthenia gravis (MG), chronic inflammatory bowel disease (IBD), type 1 diabetes (T1D), autoimmune thyroid disease, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriasis, vasculitis, and antiphospholipid syndrome (APS), on pregnancy in women. This review investigates the risk to the offspring of the women; that is, whether the mother's disease may affect fertility or disturb fetal development.

Pyroptosis, a programmed form of inflammatory cell death, has been demonstrated to participate in both Acute pancreatitis (AP) and its complication liver injury. Transgelin-2 (TAGLN2), an actin-binding protein involved in inflammatory response, has been reported to be highly expressed in AP. However, the role of TAGLN2 in AP-induced liver injury remains unclear. Mice were treated with cerulein to construct the AP model in vivo, while Kupffer cells were stimulated with lipopolysaccharide (LPS) to mimic in vitro model. A series of in vitro and in vivo experiments were performed to investigate the role and mechanism of TAGLN2 in AP-induced liver injury. Cerulein administration induced pathological injury of the pancreatic and liver tissues, along with elevated levels of amylase, lipase, alanine aminotransferase (ALT), and aspartate transaminase (AST). TAGLN2 was significantly elevated at both the transcriptional and translational levels in the hepatocytes and Kupffer cells of AP mice. Knockout of TAGLN2 alleviated liver injury by reducing inflammatory cytokine levels, pyroptosis-related protein expression, and liver dysfunction markers. The relative levels of inflammatory factors, the expressions of pyroptosis-related proteins, and the pyroptosis rate were increased in LPS-induced Kupffer cells in an in vitro model, whereas TAGLN2 knockdown reversed these changes. Mechanistically, TAGLN2 promoted activation of the ANXA2/NF-κB axis in Kupffer cells, contributing to the inflammatory response. TAGLN2 exacerbates AP-induced liver injury by enhancing hepatocyte pyroptosis through Kupffer cell-mediated inflammatory activation of the ANXA2/NF-κB axis. Targeting TAGLN2 may offer a potential therapeutic strategy for mitigating liver injury in AP.