The flower of Inula britannica contains various phenolic compounds with prophylactic properties. This study aimed to determine the anti-adipogenic effect of an I. britannica flower aqueous extract (IAE) and its underlying mechanisms in the 3T3-L1 preadipocytes and to identify the phenolic compounds in the extract. Treatment with IAE inhibited the adipogenesis of 3T3-L1 preadipocytes by showing a dose-dependently suppressed intracellular lipid accumulation and significantly mitigated expression levels of lipogenesis- and adipogenesis-associated biomarkers including transcription factors. IAE exerted an anti-adipogenic effect through the modulation of the early phases of adipogenesis including mitotic clonal expansion (MCE). Treatment with IAE inhibited MCE by arresting the cell cycle at the G0/G1 phase and suppressing the activation of MCE-related transcription factors. Furthermore, IAE inhibited adipogenesis by regulating the extracellular signal-regulated kinase 1/2 and Akt signaling pathways. Protocatechuic acid, chlorogenic acid, kaempferol-3-O-glucoside, and 6-methoxyluteolin, which are reported to exhibit anti-adipogenic properties, were detected in IAE. Therefore, modulation of early phases of adipogenesis, especially MCE, is a key mechanism underlying the anti-adipogenic activity of IAE. In summary, the anti-obesity effects of IAE can be attributed to its phenolic compounds, and hence, IAE can be used for the development of anti-obesity products.

The purpose of this study is to evaluate Lactobacillus paracasei SMB092 as a prophylactic agent for oral pathogens. We examined the physical interaction of SMB092 with a host by identifying the presence of mucus-binding (MuB) protein domains and the capacity of the mucin binding. We determined the role of heat-killed SMB092 in host oral immunity by quantifying the mRNA levels of β-defensins (BDs), Toll-like receptors (TLRs), and their cofactors (CD14/CD36) in normal human oral keratinocytes (HOK-16B cells). To assess the clinically relevant oral health effects of heat-killed SMB092, the growth of Porphyromonas (P.) gingivalis and the production of a volatile sulfur compound (H₂S) were also measured in the filtered condition media (FCM) obtained from its cultures with HOK-16B cells. SMB092 possessed 14 putative MuB protein domains and was attached to mucin. Significant amounts of hBD1/2 and TLR2/6 were expressed in heat-killed SMB092-treated HOK-16B cells. The specific neutralization of TLR2 attenuated the expression of hBD1/2 and CD14/CD36. The FCM inhibited the growth of P. gingivalis and the production of H₂S. Our data indicate that heat-killed SMB092 may contribute to a healthy oral microbiome as an immune stimulant in the production of BDs via the activation of the TLR2/6 signaling pathway.

Introductory paragraph: While CAR T cells have altered the treatment landscape for B cell malignancies, the risk of on-target, off-tumor toxicity has hampered their development for solid tumors because most target antigens are shared with normal cells ^1,2 . Researchers have attempted to apply Boolean logic gating to CAR T cells to prevent on-target, off-tumor toxicity ^3–7 ; however, a truly safe and effective logic-gated CAR has remained elusive ⁸ . Here, we describe a novel approach to CAR engineering in which we replace traditional ITAM-containing CD3ζ domains with intracellular proximal T cell signaling molecules. We demonstrate that certain proximal signaling CARs, such as a ZAP-70 CAR, can activate T cells and eradicate tumors in vivo while bypassing upstream signaling proteins such as CD3ζ. The primary role of ZAP-70 is to phosphorylate LAT and SLP-76, which form a scaffold for the propagation of T cell signaling. We leveraged the cooperative role of LAT and SLP-76 to engineer L ogic-gated I ntracellular N etwor K (LINK) CAR, a rapid and reversible Boolean-logic AND-gated CAR T cell platform that outperforms other systems in both efficacy and the prevention of on-target, off-tumor toxicity. LINK CAR will dramatically expand the number and types of molecules that can be targeted with CAR T cells, enabling the deployment of these powerful therapeutics for solid tumors and diverse diseases such as autoimmunity ⁹ and fibrosis ¹⁰ . In addition, this work demonstrates that the internal signaling machinery of cells can be repurposed into surface receptors, a finding that could have broad implications for new avenues of cellular engineering.