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Fourier-transform infrared spectroscopy (FT-IR) spectra of steam-exploded lignin (SEL) and four fractions (SEL-F1, SEL-F2, SEL-F3, and SEL-F4).
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Cosmetic ingredients originating from natural resources have garnered considerable attention, and the demand for whitening ingredients is increasing, particularly in Asian countries. Lignin is a natural phenolic biopolymer significantly effective as a natural sunscreen, as its ultraviolet protection efficacy ranges from 250 to 400 nm. However, usin...
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Context 1
... is a useful approach for studying various functional groups as well as the conformational properties of lignin. The FT-IR spectra of SEL, SEL-F1, SEL-F2, SEL-F3, and SEL-F4 are shown in Figure 2. A wide absorption band at 3360 cm −1 was assigned to the O-H stretching vibration in the aromatic and aliphatic -OH groups, whereas the bands at 2918 and 2849 cm −1 originated from the symmetric and asymmetric C-H vibrations in the methyl and methylene groups. ...
Context 2
... is a useful approach for studying various functional groups as well as the conformational properties of lignin. The FT-IR spectra of SEL, SEL-F1, SEL-F2, SEL-F3, and SEL-F4 are shown in Figure 2. A wide absorption band at 3360 cm −1 was assigned to the O-H stretching vibration in the aromatic and aliphatic -OH groups, whereas the bands at 2918 and 2849 cm −1 originated from the symmetric and asymmetric C-H vibrations in the methyl and methylene groups. ...
Context 3
... lignin is a three-dimensional amorphous biopolymer biosynthesized by the radical polymerization of monolignols (coniferyl, sinapyl, and p-coumaryl alcohols) to produce G, S, and H units, respectively [19]. In this study, several types of G, S, Figure 2. Fourier-transform infrared spectroscopy (FT-IR) spectra of steam-exploded lignin (SEL) and four fractions (SEL-F1, SEL-F2, SEL-F3, and SEL-F4). ...
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Glucagon-stimulated hepatic gluconeogenesis contributes to endogenous glucose production during fasting. Recent studies suggest that TGF-β is able to promote hepatic gluconeogenesis in mice. However, the physiological relevance of serum TGF-β levels to human glucose metabolism and the mechanism by which TGF-β enhances gluconeogenesi...
Citations
... As shown in Figure 4b, the stretching vibration for hydroxyl is observed at 3422 cm −1 [70]. The stretching vibrations for the lignin aromatic ring skeleton at 1600 cm −1 and 1507 cm −1 can be seen in all testing samples; this indicates that no significant change in the aromatic ring structure of MWL occurred during the SDES treatments [34,71]. The peak at 2936 cm −1 was attributed to the C-H vibration in CH 3 -/CH 2 = groups. ...
Deep eutectic solvents (DESs) are promising for lignin dissolution and extraction. However, they usually possess high polarity and are difficult to recycle. To overcome this drawback, a variety of switchable ionic liquids (SILs) composed of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and alcohols was synthesized and screened. According to the thermodynamic modeling suggestions, the selected DBU–HexOH SIL was coupled with hydrogen-bond donors to form switchable-DES (SDES) systems with moderated viscosity, conductivity, and pH while maintaining switchability. The SDESs produced a well-improved lignin and lignin model compound solubility compared with those of SILs; charging CO2 into SDES (SDESCO2) caused a further increase in solubility. The solubility (25 °C) of syringic acid, ferulic acid, and milled wood lignin in SDESCO2 reached 230.57, 452.17, and 279.12 mg/g, respectively. Such SDES-dissolved lignin can be regenerated using acetone as an anti-solvent. The SDES-regenerated lignin exhibited a well-preserved structure with no noticeable chemical modifications. Furthermore, the SDESCO2 lignin possessed a higher molecular weight (Mw = 10,340 g/mol; Mn = 7672 g/mol), improved uniformity (polydispersity index = 1.35), and a higher guaiacyl lignin unit content compared with the original milled wood lignin. The SDES system proposed in the present work could benefit the fractionation of lignin compounds and facilitate downstream industrial processes.
... This leads to an increase in cAMP levels, which, in turn, upregulates the MITF gene expression. The subsequent increase in MITF protein production positively influences the expressions of TYR and TRPs, which ultimately leads to elevated melanin synthesis [7,8]. Furthermore, the MAPK family proteins can increase MITF expression and the subsequent expression of melanogenesis enzymes in a similar fashion. ...
... The PKA/CREB signaling pathway plays a critical role in melanogenesis, as PKA can be activated by increased cellular cAMP, which leads to CREB phosphorylation and the subsequent upregulation of MITF transcriptional activity, which results in the expressions of tyrosinase, TRP-1, and TRP-2 [7,8]. To investigate whether 6-methylcoumarin's effect on melanin synthesis is mediated by the PKA/CREB signaling pathway, Western blot experiments were performed to determine whether the PKA and CREB phosphorylation were increased. ...
We investigated the effects of four coumarin derivatives, namely, 6-methylcoumarin, 7-methylcoumarin, 4-hydroxy-6-methylcoumarin, and 4-hydroxy-7-methylcoumarin, which have similar structures on melanogenesis in a murine melanoma cell line from a C57BL/6J mouse called B16F10. Our results showed that only 6-methylcoumarin significantly increased the melanin synthesis in a concentration-dependent manner. In addition, the tyrosinase, TRP-1, TRP-2, and MITF protein levels were found to significantly increase in response to 6-methylcoumarin in a concentration-dependent manner. To elucidate the molecular mechanism whereby 6-methylcoumarin-induced melanogenesis influences the melanogenesis-related protein expression and melanogenesis-regulating protein activation, we further assessed the B16F10 cells. The inhibition of the ERK, Akt, and CREB phosphorylation, and conversely, the increased p38, JNK, and PKA phosphorylation activated the melanin synthesis via MITF upregulation, which ultimately led to increased melanin synthesis. Accordingly, 6-methylcoumarin increased the p38, JNK, and PKA phosphorylation in the B16F10 cells, whereas it decreased the phosphorylated ERK, Akt, and CREB expressions. In addition, the 6-methylcoumarin activated GSK3β and β-catenin phosphorylation and reduced the β-catenin protein level. These results suggest that 6-methylcoumarin stimulates melanogenesis through the GSK3β/β-catenin signal pathway, thereby affecting the pigmentation process. Finally, we tested the safety of 6-methylcoumarin for topical applications using a primary human skin irritation test on the normal skin of 31 healthy volunteers. We found that 6-methylcoumarin did not cause any adverse effects at concentrations of 125 and 250 μM. Our findings indicate that 6-methylcoumarin may be an effective pigmentation stimulator for use in cosmetics and the medical treatment of photoprotection and hypopigmentation disorders.
Currently, ERY974, a humanized IgG4 bispecific T cell-redirecting antibody recognizing glypican-3 and CD3, is in phase I clinical trials. After a first-in-human clinical trial of an anti-CD28 agonist monoclonal antibody resulting in severe life-threatening adverse events, the minimal anticipated biological effect level approach has been considered for determining the first-in-human dose of high-risk drugs. Accordingly, we aimed to determine the first-in-human dose of ERY974 using both the minimal anticipated biological effect level and no observed adverse effect level approaches. In the former, we used the 10% effective concentration value from a cytotoxicity assay using the huH-1 cell line with the highest sensitivity to ERY974 to calculate the first-in-human dose of 4.9 ng/kg, at which maximum drug concentration after 4 h of intravenous ERY974 infusion was equal to the 10% effective concentration value. To determine the no observed adverse effect level, we conducted a single-dose study in cynomolgus monkeys that were intravenously infused with ERY974 (0.1, 1, and 10 μg/kg). The lowest dose of 0.1 μg/kg was determined as the no observed adverse effect level, and the first-in-human dose of 3.2 ng/kg was calculated, considering body surface area and species difference. For the phase I clinical trial, we selected 3.0 ng/kg as a starting dose, which was lower than the first-in-human dose calculated from both the no observed adverse effect level and minimal anticipated biological effect level. Combining these two methods to determine the first-in-human dose of strong immune modulators such as T cell-redirecting antibodies would be a suitable approach from safety and efficacy perspectives.
Clinical trial registration: JapicCTI-194805/NCT05022927.
