Bone morphogenetic protein 2 (BMP2), a member of the transforming growth factor-β (TGF-β) super-family, is one of the main chondrogenic growth factors involved in cartilage regeneration. BMP2 is ...known to induce chondrogenic differentiation in various types of stem cells in vitro. However, BMP2 also induces osteogenic differentiation and endochondral ossification in mesenchymal stem cells (MSCs). Although information regarding BMP2-induced chondrogenic and osteogenic differentiation within the same system might be essential for cartilage tissue engineering, few studies concerning these issues have been conducted. In this study, BMP2 was identified as a regulator of chondrogenic differentiation, osteogenic differentiation and endochondral bone formation within the same system. BMP2 was used to regulate chondrogenic and osteogenic differentiation in stem cells within the same culture system in vitro and in vivo. Any changes in the differentiation markers were assessed. BMP2 was found to induce chondrogenesis and osteogenesis in vitro via the expression of Sox9, Runx2 and its downstream markers. According to the results of the subcutaneous stem cell implantation studies, BMP2 not only induced cartilage formation but also promoted endochondral ossification during ectopic bone/cartilage formation. In fetal limb cultures, BMP2 promoted chondrocyte hypertrophy and endochondral ossification. Our data reveal that BMP2 can spontaneously induce chondrogenic differentiation, osteogenic differentiation and endochondral bone formation within the same system. Thus, BMP2 can be used in cartilage tissue engineering to regulate cartilage formation but has to be properly regulated for cartilage tissue engineering in order to retain the cartilage phenotype.
An efficient and practical approach for the synthesis of medicinally important acridones was developed from anthranils and commercially available arylboronic acids by a tandem copper(
i
)-catalyzed ...electrophilic amination/Ag(
i
)-mediated oxidative annulation strategy. This new and straightforward protocol displayed a broad substrate scope (25 examples) and high functional group tolerance. What's more, a possible mechanistic proposal was also presented.
An efficient and practical approach for the synthesis of medicinally important acridones was developed from anthranils and arylboronic acids by a tandem copper(
i
)-catalyzed electrophilic amination/Ag(
i
)-mediated oxidative annulation strategy.
The rational design of highly efficient, low-cost, and durable electrocatalysts to replace platinum-based electrodes for oxygen reduction reaction (ORR) is highly desirable. Although atomically ...dispersed supported metal catalysts often exhibit excellent catalytic performance with maximized atom efficiency, the fabrication of single-atom catalysts remains a great challenge because of their easy aggregation. Herein, a simple ionothermal method was developed to fabricate atomically dispersed Fe–N x species on porous porphyrinic triazine-based frameworks (FeSAs/PTF) with high Fe loading up to 8.3 wt %, resulting in highly reactive and stable single-atom ORR catalysts for the first time. Owing to the high density of single-atom Fe–N4 active sites, highly hierarchical porosity, and good conductivity, the as-prepared catalyst FeSAs/PTF-600 exhibited highly efficient activity, methanol tolerance, and superstability for oxygen reduction reaction (ORR) under both alkaline and acidic conditions. This work will bring new inspiration to the design of highly efficient noble-metal-free catalysts at the atomic scale for energy conversion.
Display omitted
•Water-extracted polysaccharides from M. albuminosa (MAWP) were purified into three sub-fractions.•Three purified fractions exhibited significant polysaccharide structural ...heterogeneity.•MAWP contained glucomannogalactans and galactoglucans with different viscosity.•Three fractions adapted random coil conformation in aqueous solution.
Macrolepiota albuminosa (Berk.) Pegler is abundant in active polysaccharides, but little is known about their structures and solution properties. In this study, water-extracted polysaccharides from M. albuminosa (MAWP) were purified into three fractions with structural heterogeneity, which was attributed to the diversity in molecular weight, monosaccharide composition and linkage patterns, further affecting their solution properties. Methylation and NMR analysis revealed MAWP-60p and MAWP-70 were a 3-O-methylated glucomannogalactan and a previously unreported glucomannogalactan, whereas MAWP-80 was elucidated as a branched galactoglucan. Besides, three fractions exhibited random coil conformation in aqueous solution, while MAWP-60p had the highest viscosity due to its highest molecular weight, mean square radius of gyration (Rg) and O-methyl group attached to the backbone. The molecular weight, monosaccharide composition and glycosidic linkages might be the major contributors to the flexibility, molecular size and stereochemistry of mushroom polysaccharide chains.
This study aimed to establish an effective prognostic nomogram with or without plasma Epstein-Barr virus DNA (EBV DNA) for nondisseminated nasopharyngeal carcinoma (NPC).
The nomogram was based on a ...retrospective study of 4630 patients who underwent radiotherapy with or without chemotherapy at Sun Yat-sen University Cancer Center from 2007 to 2009. The predictive accuracy and discriminative ability of the nomogram were determined by a concordance index (C-index) and calibration curve and were compared with EBV DNA and the current staging system. The results were validated using bootstrap resampling and a prospective cohort study on 1819 patients consecutively enrolled from 2011 to 2012 at the same institution. All statistical tests were two-sided.
Independent factors derived from multivariable analysis of the primary cohort to predict recurrence were age, sex, body mass index (BMI), T stage, N stage, plasma EBV DNA, pretreatment high sensitivity C-reactive protein (hs-CRP), lactate dehydrogenase (LDH), and hemoglobin level (HGB), which were all assembled into the nomogram with (nomogram B) or without EBV DNA (nomogram A). The calibration curve for the probability of recurrence showed that the nomogram-based predictions were in good agreement with actual observations. The C-index of nomogram B for predicting recurrence was 0.728 (P < .001), which was statistically higher than the C-index values for nomogram A (0.690), EBV DNA (0.680), and the current staging system (0.609). The C-index of nomogram B (0.730) and nomogram A (0.681) remained higher for predicting recurrence among patients treated with intensity-modulated radiotherapy (P < .001). The results were confirmed in the validation cohort.
The proposed nomogram with or without plasma EBV DNA resulted in more accurate prognostic prediction for NPC patients.
Highly evolutionarily conserved multiprotein complexes termed Complex of Proteins Associated with Set1 (COMPASS) are required for histone 3 lysine 4 (H3K4) methylation.
Set1, Trx, and Trr form the ...core subunits of these complexes. We show that flies deficient in any of these three subunits demonstrated high lethality at eclosion (emergence of adult flies from their pupal cases) and significantly shortened lifespans for the adults that did emerge. Silencing
,
, or
in the heart led to a reduction in H3K4 monomethylation (H3K4me1) and dimethylation (H3K4me2), reflecting their distinct roles in H3K4 methylation. Furthermore, we studied the gene expression patterns regulated by Set1, Trx, and Trr. Each of the COMPASS core subunits controls the methylation of different sets of genes, with many metabolic pathways active early in development and throughout, while muscle and heart differentiation processes were methylated during later stages of development. Taken together, our findings demonstrate the roles of COMPASS series complex core subunits Set1, Trx, and Trr in regulating histone methylation during heart development and, given their implication in congenital heart diseases, inform research on heart disease.
Previous studies have shown that glycogen synthase kinase 3β (GSK3β) suppression is a potential strategy for human acute myeloid leukemia (AML) therapy. However, the cytotoxic mechanism associated ...with GSK3β suppression remains unresolved. Thus, the underlying mechanism of N‐(4‐methoxybenzyl)‐N′‐(5‐nitro‐1,3‐thiazol‐2‐yl)urea (AR‐A014418)‐elicited GSK3β suppression in the induction of AML U937 and HL‐60 cell death was investigated in this study. Our study revealed that AR‐A014418‐induced MCL1 downregulation remarkably elicited apoptosis of U937 cells. Furthermore, the AR‐A014418 treatment increased p38 MAPK phosphorylation and decreased the phosphorylated Akt and ERK levels. Activation of p38 MAPK subsequently evoked autophagic degradation of 4EBP1, while Akt inactivation suppressed mTOR‐mediated 4EBP1 phosphorylation. Furthermore, AR‐A014418‐elicited ERK inactivation inhibited Mnk1‐mediated eIF4E phosphorylation, which inhibited MCL1 mRNA translation in U937 cells. In contrast to GSK3α, GSK3β downregulation recapitulated the effect of AR‐A014418 in U937 cells. Transfection of constitutively active GSK3β or cotransfection of constitutively activated MEK1 and Akt suppressed AR‐A014418‐induced MCL1 downregulation. Moreover, AR‐A014418 sensitized U937 cells to ABT‐263 (BCL2/BCL2L1 inhibitor) cytotoxicity owing to MCL1 suppression. Collectively, these results indicate that AR‐A014418‐induced GSK3β suppression inhibits ERK–Mnk1–eIF4E axis‐modulated de novo MCL1 protein synthesis and thereby results in U937 cell apoptosis. Our findings also indicate a similar pathway underlying AR‐A014418‐induced death in human AML HL‐60 cells.
Suppression of glycogen synthase kinase 3β (GSK3β) by AR‐A014418 simultaneously evokes inactivation of Akt/mTOR pathway‐mediated 4EBP1 phosphorylation, inactivation of ERK/Mnk1‐mediated eIF4E phosphorylation, and activation of p38 MAPK‐mediated 4EBP1 degradation in U937 cells. The interplay of ERK‐, Akt‐ and p38 MAPK‐mediated pathways modulates MCL1 expression in AR‐A014418‐treated U937 cells.
•Inhibition of bacterial growth by EGCG is not attributed to its H2O2 production.•EGCG increase intracellular ROS and induce adaptive oxidative stress response.•Inhibition of bacterial growth by EGCG ...was blunted by NAC.•EGCG increased bacterial lethality of paraquat with synergistic effect.
The antibacterial effects of tea polyphenol epigallocatechin gallate (EGCG), a common phytochemical with a number of potential health benefits, are well known. However, the mechanism of its bactericidal action remains unclear. Using E. coli as a model organism, it is argued here that H2O2 synthesis by EGCG is not attributed to its inhibitory effects. In contrast, the bactericidal action of EGCG was a result of increased intracellular reactive oxygen species and blunted adaptive oxidative stress response in E. coli due to the co-administration of antioxidant N-acetylcysteine, and not on account of exogenous catalase. Furthermore, we noted a synergistic bactericidal effect for EGCG when combined with paraquat. However, under anaerobic conditions, the inhibitory effect of EGCG was prevented. In conclusion, EGCG caused an increase in endogenous oxidative stress in E. coli, thereby inhibiting its growth, and hence the use of EGCG as a prooxidant is supported by this study.
PDF
