Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme that plays a pivotal role in immune regulation by metabolizing tryptophan into kynurenine, leading to T cell suppression and promoting immune tolerance. However, persistent activation of IDO1 can lead to prolonged immune stimulation in inflammatory conditions such as skin diseases and chronic inflammation. In this study, we developed modified peptide nucleic acids (PNAs) conjugated with cationic lipid chains to target IDO1 pre-mRNA and evaluated their anti-inflammatory effects in human keratinocytes. The modified PNAs demonstrated enhanced solubility, robust binding affinity, and effective penetration into keratinocytes. Quantitative PCR results showed significant downregulation of IDO1 and pro-inflammatory cytokines such as IL-6, IL-8, and PTGS2 in interferon γ (IFNγ)-treated keratinocytes. These findings suggest that cell-penetrating PNAs targeting IDO1 hold potential as a therapeutic approach for inflammatory skin disorders and chronic inflammation.

Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme that plays a pivotal role in immune regulation by metabolizing tryptophan into kynurenine, leading to T cell suppression and promoting immune tolerance. However, persistent activation of IDO1 can lead to prolonged immune stimulation in inflammatory conditions such as skin diseases and chronic inflammation. In this study, we developed modified peptide nucleic acids (PNAs) conjugated with cationic lipid chains to target IDO1 pre-mRNA and evaluated their anti-inflammatory effects in human keratinocytes. The modified PNAs demonstrated enhanced solubility, robust binding affinity, and effective penetration into keratinocytes. Quantitative PCR results showed significant downregulation of IDO1 and pro-inflammatory cytokines such as IL-6, IL-8, and PTGS2 in interferon γ (IFNγ)-treated keratinocytes. These findings suggest that cell-penetrating PNAs targeting IDO1 hold potential as a therapeutic approach for inflammatory skin disorders and chronic inflammation.

Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme that plays a pivotal role in immune regulation by metabolizing tryptophan into kynurenine, leading to T cell suppression and promoting immune tolerance. However, persistent activation of IDO1 can lead to prolonged immune stimulation in inflammatory conditions such as skin diseases and chronic inflammation. In this study, we developed modified peptide nucleic acids (PNAs) conjugated with cationic lipid chains to target IDO1 pre-mRNA and evaluated their anti-inflammatory effects in human keratinocytes. The modified PNAs demonstrated enhanced solubility, robust binding affinity, and effective penetration into keratinocytes. Quantitative PCR results showed significant downregulation of IDO1 and pro-inflammatory cytokines such as IL-6, IL-8, and PTGS2 in interferon γ (IFNγ)-treated keratinocytes. These findings suggest that cell-penetrating PNAs targeting IDO1 hold potential as a therapeutic approach for inflammatory skin disorders and chronic inflammation.

Skin aging results from complex interactions of intrinsic and extrinsic factors, leading to structural and biochemical changes such as wrinkles and dryness. Ultraviolet (UV) irradiation leads to the degradation of hyaluronic acid (HA) in the skin, and the fragmented HA contributes to inflammation. This study revealed that the synergistic combination of carnosine and retinol (ROL) increases HA production in normal human epidermal keratinocytes (NHEKs) by upregulating hyaluronan synthase 2 (HAS2) gene transcription. Simultaneously, the combined treatment of carnosine and ROL significantly attenuates UVB-induced prostaglandin E2 (PGE2) synthesis in NHEKs. A significant correlation exists between the increase of HA synthesis and the inhibition of PGE2 production. This study suggests that combined treatment of carnosine and ROL can improve skin aging phenotypes associated with UVB irradiation.

Sesquiterpene lactones, a class of natural compounds abundant in the Asteraceae family, have gained attention owing to their diverse biological activities, and particularly their anti-proliferative effects on human cancer cells. In this study, we systematically investigated the structure-activity relationship of ten sesquiterpene lactones with the aim of elucidating the structural determinants for the STAT3 inhibition governing their anti-proliferative effects. Our findings revealed a significant correlation between the STAT3 inhibitory activity and the anti-proliferative effects of sesquiterpene lactones in MDA-MB-231 breast cancer cell lines. Among the compounds tested, alantolactone and isoalantolactone emerged as the most potent STAT3 inhibitors, highlighting their potential as candidates for anticancer drug development. Through protein-ligand docking studies, we revealed the structural basis of STAT3 inhibition by sesquiterpene lactones, emphasizing the critical role of hydrogen-bonding interactions with key residues, including Arg609, Ser611, Glu612, and Ser613, in the SH2 domain of STAT3. Furthermore, our conformational analysis revealed the decisive role of the torsion angle within the geometry-optimized structures of sesquiterpene lactones in their STAT3 inhibitory activity (R=0.80, p<0.01). These findings not only provide preclinical evidence for sesquiterpene lactones as promising phytomedicines against diseases associated with abnormal STAT3 activation, but also highlight the importance of stereochemical aspects in their activity.

The natural flavonoid macakurzin C (1) exhibited adiponectin biosynthesis-inducing activity during adipogenesis in human bone marrow mesenchymal stem cells and its molecular mechanism was directly associated with a pan-peroxisome proliferator-activated receptor (PPAR) modulator affecting all three PPAR subtypes α, γ, and δ. In this study, increases in adiponectin biosynthesisinducing activity by macakurzin C derivatives (2–7) were studied. The most potent adiponectin biosynthesis-inducing compound 6, macakurzin C 3,5-dimethylether, was elucidated as a dual PPARα/γ modulator. Compound 6 may exhibit the most potent activity because of the antagonistic relationship between PPARδ and PPARγ. Docking studies revealed that the O-methylation of macakurzin C to generate compound 6 significantly disrupted PPARδ binding. Compound 6 has therapeutic potential in hypoadiponectinemia-related metabolic diseases.

The GlideScope® videolaryngoscope (GVL) is widely used in patients with difficult airways and provides a good glottic view. However, the acute angle of the blade can make insertion and advancement of an endotracheal tube (ETT) more difficult than direct laryngoscopy, and the use of a stylet is recommended. This randomized controlled trial compared Parker Flex-It™ stylet (PFS) with GlideRite® rigid stylet (GRS) to facilitate intubation with the GVL in simulated difficult intubations. Methods: Fifty-four patients were randomly allocated to undergo GVL intubation using either GRS (GRS group) or PFS (PFS group). The total intubation time (TIT), 100-mm visual analog scale (VAS) for ease of intubation, success rate at the first attempt, use of laryngeal manipulation, tube advancement rate by assistant, and complications were recorded. Results: There was no significant difference between the GRS and PFS groups regarding TIT (50.3 ± 12.0 s in the GRS group and 57.8 ± 18.8 s in the PFS group, P = 0.108). However, intubation was more difficult in the PFS group than in the GRS group according to VAS score (P = 0.011). Cases in which the ETT was advanced from the stylet by an assistant, were more frequent in the GRS group than in the PFS group (P = 0.002). The overall incidence of possible complications was not significantly different. Conclusions: In patients with a simulated difficult airway, there was no difference in TIT using either the PFS or GRS. However, endotracheal intubation with PFS is more difficult to perform than GRS.