Even when the policy rate is currently not constrained by its effective lower bound (ELB), the possibility that the policy rate will become constrained in the future lowers today's inflation by creating tail risk in future inflation and thus reducing expected inflation. In an empirically rich model calibrated to match key features of the U.S. economy, we find that the tail risk induced by the ELB causes inflation to undershoot the target rate of 2 percent by as much as 45 basis points at the economy's risky steady state. Our model suggests that achieving the inflation target may be more difficult now than before the Great Recession, if the recent ELB experience has led households and firms to revise up their estimate of the ELB frequency.

Even when the policy rate is currently not constrained by its effective lower bound (ELB), the possibility that the policy rate will become constrained in the future lowers today's inflation by creating tail risk in future inflation and thus reducing expected inflation. In an empirically rich model calibrated to match key features of the U.S. economy, we find that the tail risk induced by the ELB causes inflation to undershoot the target rate of 2 percent by as much as 50 basis points at the economy's risky steady state. Our model suggests that achieving the inflation target may be more difficult now than before the Great Recession, if the likely decline in long-run neutral rates has led households and firms to revise up their estimate of the frequency of future ELB events.

The Galectin-Related Protein (GRP), encoded by the LGALSL gene, assigned to the protein family of β-galactoside-binding Galectins, has lost carbohydrate-binding abilities. Its chicken homolog (C-GRP) occurs in the bursa of Fabricius’ epithelial and B cells. Our study investigates the unknown regulatory mechanisms controlling its expression by analyzing the promoter region of the chicken (C-)LGALSL gene in chicken cells. We aimed to identify the sequence elements of the C-LGALSL gene promoter responsible for maximum activity and transcription factors (TFs) that can modulate this activity. Using luciferase reporter assays, we investigated deletion variants of the 5′ region (−2480 bp to +26 bp). Through in silico analyses and site-directed mutagenesis, we explored potential transcription factor binding sites, identified crucial transcription factors through transient overexpression and tested its direct binding by ChIP. Our findings highlight that the region from −274 to −75 bp, conserved among bird species, is crucial for promoter regulation. Among other tested factors, only the chicken (ch) Krüppel-like factors, chKLF3 and chKLF7, modulate the promoter’s activity. The TFs chKLF3 acts as a repressor, and chKLF7 as an activator, although direct binding could not be confirmed. In conclusion, chKLF3 and chKLF7 contribute, in contrast to other factors with binding sites in the region from −274 to −75 bp, to C-LGALSL gene promoter regulation with a balanced impact on activity.

Background/Objectives: Galectins contribute to the pathogenesis of osteoarthritis (OA) by amplifying inflammatory and catabolic signaling, yet targeted therapeutic approaches remain limited. Three Dimensional (3D) models offer a promising platform to study human OA pathophysiology and evaluate novel interventions. Methods: We established 3D pellet cultures derived from human OA chondrocytes to investigate galectin-induced extracellular matrix (ECM) remodeling and the chondroprotective potential of phytochemicals. OA pellets were stimulated with individual galectins (Gal-1, -3, -4, -8) or a Gal-1/-3/-8 mixture, followed by co-treatment with Brazilin, Diacerein, Quercetin, Resveratrol, or Avocado-Soybean Unsaponifiables (ASU). Morphological, histological, biochemical, and gene expression analyses were performed to assess tissue integrity and molecular responses. Results: Galectin treatment induced pronounced pellet shrinkage, matrix depletion, and upregulation of matrix-degrading enzymes (MMP-1, MMP-3, MMP-13, ADAMTS-4), while suppressing matrix synthesis markers (COL2A1, COL1A1), highlighting their cooperative catabolic effects. Co-treatment with phytochemicals conferred differential protection: Brazilin and Diacerein most consistently preserved pellet size, reduced matrix-degrading gene expression, and attenuated pro-MMP-13 secretion. Resveratrol restored histological matrix density but failed to suppress pro-MMP-13 secretion. Notably, no phytochemical fully restored COL2A1 expression under galectin-induced stress. Conclusions: Our study identifies Brazilin, Diacerein, and Resveratrol as promising modulators of galectin-driven cartilage degeneration and demonstrates the translational potential of patient-derived chondrogenic pellets as a human-relevant platform for preclinical drug evaluation in OA. The 3D culture effectively recapitulates key aspects of OA pathophysiology and offers a robust system to advance therapeutic discovery targeting ECM remodeling.

Galectin-3 (Gal-3), a member of the β-galactoside-binding protein family, is critically involved in inflammation, extracellular matrix remodelling, and cartilage degeneration in osteoarthritis (OA). This study aims to elucidate the regulation of the human galectin-3 gene ( LGALS3 ) promoter in SW1353 cells and its control by SOX transcription factors, known to be dysregulated during OA pathogenesis. We sought to identify key sequence elements in the LGALS3 promoter responsible for its transcriptional activity and relevant transcription factors (TFs). Using luciferase reporter assays, we examined deletion variants of the 5’ region (-2638 bp to + 52 bp) and assessed their activation potential. We also identified potential transcription factor binding sites (TFBS) through in silico analyses and confirmed SOX9 binding in the − 93/+49 region by chromatin immunoprecipitation using HaloCHIP™. Functional assays revealed that the proximal promoter region (-97 bp to + 52 bp) is critical for reporter gene expression in SW1353 cells. This study demonstrates that the presence of SOX9 leads to a dose-dependent decrease in LGALS3 promoter activity in SW1353 cells. Consistent with this trend, SOX9 overexpression caused a modest reduction in endogenous LGALS3 mRNA levels. Together, these findings highlight the importance of SOX TF interactions in regulating LGALS3 expression and their potential role in chondrocytes.