Interleukin 21 (IL‑21) and its receptor, IL‑21R, play a key role in innate and adaptive immunity. In the present study, the effect of IL‑21 and IL‑21R on the pathogenesis of diffuse large B‑cell lymphoma (DLBCL) was investigated. The serum levels of IL‑21 were detected by enzyme‑linked immunosorbent assay, and the expression of IL‑21R on CD8+ T cells was examined through flow cytometry. The data showed that the serum level of IL‑21 was significantly decreased in the patients with DLBCL compared with the healthy controls (P<0.001), whereas the expression of IL‑21R was clearly elevated on the CD8+ T cells in the patients with DLBCL. Further analyses revealed that the downregulation of the IL‑21 serum level was correlated with an increased tumor stage of DLBCL, while the expression of IL‑21R on the CD8+ T cells was positively correlated with the tumor stage. Also, the serum level of IL‑21 and the proportion of IL‑21R on the CD8+ T cells were negatively correlated in the patients. Notably, it was identified that the proportion of IL‑21R on the CD8+ T cells, but not the serum level of IL‑21, was significantly upregulated in the patients with bone‑marrow involvement and B symptoms. These results indicate that IL‑21 and IL‑21R may be involved in the pathogenesis of DLBCL, in which IL‑21R may reflect the progression of the disease more accurately than the serum level of IL‑21.

Background: Acute respiratory distress syndrome (ARDS) / acute lung injury (ALI) is a serious medical disease characterized by pulmonary dysfunction and inflammation. This study aims to determine the main molecular modules linked to ARDS and investigate the role of Fibulin-1 (FBLN1) in regulating ferroptosis in ARDS. Methods: Weighted Gene Co-expression Network Analysis (WGCNA) was employed on the GSE263867 dataset to find key modules associated with ALI. Differentially expressed genes (DEGs) and protein-protein interaction (PPI) networks were analyzed. MLE-12 cells were treated with lipopolysaccharide (LPS) to induce ferroptosis. In vitro studies were conducted to investigate the effects of FBLN1 and Transforming Growth Factor Beta 1 (TGF-β) overexpression on cell viability, oxidative stress markers, and ferroptosis-related proteins. Results: WGCNA identified the turquoise module as significantly negatively correlated with ARDS. Five key overlapping genes (GRIA1, OGN, COL14A1, FBLN1, and COL6A3) were significantly downregulated in ARDS samples. LPS treatment induced ferroptosis in MLE-12 cells, indicated by increased malondialdehyde (MDA), lipid reactive oxygen species (ROS), and ferrous iron (Fe²⁺) levels, and decreased cell viability and glutathione (GSH) levels. FBLN1 overexpression partially reversed these effects. Additionally, FBLN1 inhibited the TGF-β/Smad signaling pathway, as shown by decreased TGF-β and p-Smad protein levels. TGF-β overexpression exacerbated LPS-induced oxidative stress and ferroptosis, reducing cell viability and GSH levels. FBLN1 overexpression counteracted this effect, suggesting antagonistic roles for FBLN1 and TGF-β in regulating ferroptosis. Conclusion: This study highlights FBLN1 as a critical regulator of ferroptosis in ARDS. Targeting the TGF-β/Smad pathway to modulate FBLN1 expression offers a potential therapeutic strategy to alleviate oxidative stress and mitigate pulmonary injury in inflammatory lung diseases.

Pancreatic adenocarcinoma (PAAD) is a notably aggressive malignancy with limited treatment options and an unfavorable prognosis for patients. We aimed to investigate molecular mechanisms by which Sam's pointed domain-containing ETS transcription factor (SPDEF) exerts effects on PAAD progression. We analyzed differentially expressed genes (DEGs) and their integration with ETS family members using the The Cancer Genome Atlas (TCGA) database, hence identifying SPDEF as a core gene in PAAD. Kaplan-Meier survival analysis confirmed SPDEF’s prognostic potential. In vitro experiments validated the association with cell proliferation and apoptosis, affecting pancreatic cancer cell dynamics. We detected increased SPDEF expression in PAAD tumor samples. Our in vitro studies revealed that SPDEF regulates mRNA and protein expression levels, and significantly affects cell proliferation. Moreover, SPDEF was associated with reduced apoptosis and enhanced cell migration and invasion. In-depth analysis of SPDEF-targeted genes revealed four crucial genes for advanced prognostic model, among which S100A16 was significantly correlated with SPDEF. Mechanistic analysis showed that SPDEF enhances the transcription of S100A16, which in turn enhances PAAD cell migration, proliferation, and invasion by activating the PI3K/AKT signaling pathway. Our study revealed the critical role of SPDEF in promoting PAAD by upregulating S100A16 transcription and stimulating the PI3K/AKT signaling pathway. This knowledge deepened our understanding of pancreatic cancer's molecular progression and unveiled potential therapeutic strategies targeting SPDEF-driven pathways.

Background: Ischemic stroke triggers inflammatory responses that lead to neuronal damage, with microglial polarization significantly influencing post-stroke inflammation. This study explores the role of Fc gamma receptor Ia (FCGR1A) in microglial polarization and its regulatory mechanisms in ischemic stroke. Methods: Differentially expressed genes (DEGs) associated with ischemic stroke were identified using the GSE58294 dataset. Hub genes were found by analyzing protein–protein interaction (PPI) networks. BV2 microglia were subjected to oxygen–glucose deprivation/reoxygenation (OGD/R) to mimic ischemic conditions in vitro, and FCGR1A and inflammatory marker levels were assessed. Besides, BV2 cells were stimulated with lipopolysaccharide (LPS) and interferon-gamma (IFN-γ) to induce M1 polarization, and the effects of FCGR1A overexpression and knockdown on cytokine production and microglial polarization were evaluated. The function of the AMP-activated protein kinase (AMPK)-mTOR pathway in regulating microglial polarization was further investigated using the mTOR inhibitor rapamycin (RAP). Results: From the 327 DEGs identified, FCGR1A was chosen as a hub gene. OGD/R treatment of BV2 cells produced a time-dependent rise in FCGR1A, induction of brown adipocytes 1 (Iba1), and interleukin 6 (IL-6) expression, indicating enhanced inflammation. FCGR1A overexpression induced a proinflammatory response and promoted M1 polarization, whereas FCGR1A knockdown reduced inflammation and shifted toward an anti-inflammatory M2 phenotype. Inhibition of the mTOR pathway using RAP, combined with FCGR1A knockdown, significantly enhanced AMPK activation and promoted a shift toward an anti-inflammatory M2 phenotype. Conclusion: FCGR1A modulates microglial polarization by affecting the AMPK–mTOR signaling pathway in ischemic conditions. Targeting FCGR1A and related pathways could offer new therapeutic strategies to lessen inflammation and facilitate the healing process after an ischemic stroke.