Inhibition of RANKL-Induced Osteoclastogenesis by Novel Mutant RANKL

Background: Recently, it was reported that leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4, also called GPR48) is another receptor for RANKL and was shown to compete with RANK to bind RANKL and suppress canonical RANK signaling during osteoclast differentiation. The critical role of the protein triad RANK–RANKL in osteoclastogenesis has made their binding an important target for the development of drugs against osteoporosis. In this study, point-mutations were introduced in the RANKL protein based on the crystal structure of the RANKL complex and its counterpart receptor RANK, and we investigated whether LGR4 signaling in the absence of the RANK signal could lead to the inhibition of osteoclastogenesis.; Methods: The effects of point-mutated RANKL (mRANKL-MT) on osteoclastogenesis were assessed by tartrate-resistant acid phosphatase (TRAP), resorption pit formation, quantitative real-time polymerase chain reaction (qPCR), western blot, NFATc1 nuclear translocation, micro-CT and histomorphological assay in wild type RANKL (mRANKL-WT)-induced in vitro and in vivo experimental mice model. Results: As a proof of concept, treatment with the mutant RANKL led to the stimulation of GSK-3β phosphorylation, as well as the inhibition of NFATc1 translocation, mRNA expression of TRAP and OSCAR, TRAP activity, and bone resorption, in RANKL-induced mouse models; and Conclusions: The results of our study demonstrate that the mutant RANKL can be used as a therapeutic agent for osteoporosis by inhibiting RANKL-induced osteoclastogenesis via comparative inhibition of RANKL. Moreover, the mutant RANKL was found to lack the toxic side effects of most osteoporosis treatments.     

Lithiophilic MXene-Guided Lithium Metal Nucleation and Growth Behavior

The positive effects of a lithiophilic substrate on the electrochemical performance of lithium metal anodes are confirmed in several reports, while the understanding of lithiophilic substrate-guided lithium metal nucleation and growth behavior is still insufficient. In this study, the effect of a lithiophilic surface on lithium metal nucleation and growth behaviors is investigated using a large-area Ti₃C₂T_x MXene substrate with a large number of oxygen and fluorine dual heteroatoms. The use of the MXene substrate results in a high lithium-ion concentration as well as the formation of uniform solid–electrolyte-interface (SEI) layers on the lithiophilic surface. The solid–solid interface (MXene-SEI layer) significantly affects the surface tension of the deposited lithium metal nuclei as well as the nucleation overpotential, resulting in the formation of uniformly dispersed lithium nanoparticles ( ≈ 10–20 nm in diameter) over the entire MXene surface. The primary lithium nanoparticles preferentially coalesce and agglomerate into larger secondary particles while retaining their primary particle shapes. Subsequently, they form close-packed structures, resulting in a dense metal layer composed of particle-by-particle microstructures. This distinctive lithium metal deposition behavior leads to highly reversible cycling performance with high Columbic efficiencies >  99.0% and long cycle lives of over 1000 cycles.     

Anticancer activity of flavonoids accompanied by redox state modulation and the potential for a chemotherapeutic strategy

Since researchers began studying the mechanism of flavonoids’ anticancer activity, little attention has been focused on the modulation of redox state in cells as a potential chemotherapeutic strategy. However, recent studies have begun identifying that the anticancer effect of flavonoids occurs both in their antioxidative activity which scavenges ROS and their prooxidative activity which generates ROS. Against this backdrop, this study attempts to achieve a comprehensive analysis of the individual and separate study findings regarding flavonoids’ modulation of redox state in cancer cells. It focuses on the mechanism behind the anticancer effect, and mostly on the modulation of redox potential by flavonoids such as quercetin, hesperetin, apigenin, genistein, epigallocatechin-3-gallate (EGCG), luteolin and kaempferol in both in vitro and animal models. In addition, the clinical applications of and bioavailability of flavonoids were reviewed to help build a treatment strategy based on flavonoids’ prooxidative potential.     

Validation of avenanthramide and other phenolic compounds in oats and sprouted oats and their antimicrobial properties against Escherichia coli O157:H7

Food Science and Biotechnology - Oat contains a variety of phenolic compounds, including avenanthramides, which are found only in oats. This study was conducted to establish the quantitative...     

Capsiate Intake with Exercise Training Additively Reduces Fat Deposition in Mice on a High-Fat Diet,but Not without Exercise Training

While exercise training (ET) is an efficient strategy to manage obesity, it is recommended with a dietary plan to maximize the antiobesity functions owing to a compensational increase in energy intake. Capsiate is a notable bioactive compound for managing obesity owing to its capacity to increase energy expenditure. We aimed to examine whether the antiobesity effects of ET can be further enhanced by capsiate intake (CI) and determine its effects on resting energy expenditure and metabolic molecules. Mice were randomly divided into four groups (n = 8 per group) and fed high-fat diet. Mild-intensity treadmill ET was conducted five times/week; capsiate (10 mg/kg) was orally administered daily. After 8 weeks, resting metabolic rate and metabolic molecules were analyzed. ET with CI additively reduced the abdominal fat rate by 18% and solely upregulated beta-3-adrenoceptors in adipose tissue (p = 0.013) but did not affect the metabolic molecules in skeletal muscles. Surprisingly, CI without ET significantly increased the abdominal fat rate (p = 0.001) and reduced energy expenditure by 9%. Therefore, capsiate could be a candidate compound for maximizing the antiobesity effects of ET by upregulating beta-3-adrenoceptors in adipose tissue, but CI without ET may not be beneficial in managing obesity.     

Effects of Electromagnetic Waves with LTE and 5G Bandwidth on the Skin Pigmentation In Vitro

With the rapid growth of wireless communication devices, the influences of electromagnetic fields (EMF) on human health are gathering increasing attention. Since the skin is the largest organ of the body and is located at the outermost layer, it is considered a major target for the health effects of EMF. Skin pigmentation represents one of the most frequent symptoms caused by various non-ionizing radiations, including ultraviolet radiation, blue light, infrared, and extremely low frequency (ELF). Here, we investigated the effects of EMFs with long-term evolution (LTE, 1.762 GHz) and 5G (28 GHz) bandwidth on skin pigmentation in vitro. Murine and Human melanoma cells (B16F10 and MNT-1) were exposed to either LTE or 5G for 4 h per day, which is considered the upper bound of average smartphone use time. It was shown that neither LTE nor 5G exposure induced significant effects on cell viability or pigmentation. The dendrites of MNT-1 were neither lengthened nor regressed after EMF exposure. Skin pigmentation effects of EMFs were further examined in the human keratinocyte cell line (MNT-1-HaCaT) co-culture system, which confirmed the absence of significant hyper-pigmentation effects of LTE and 5G EMFs. Lastly, MelanoDerm™, a 3D pigmented human epidermis model, was irradiated with LTE (1.762 GHz) or 5G (28 GHz), and image analysis and special staining were performed. No changes in the brightness of MelanoDerm™ tissues were observed in LTE- or 5G-exposed tissues, except for only minimal changes in the size of melanocytes. Collectively, these results imply that exposure to LTE and 5G EMFs may not affect melanin synthesis or skin pigmentation under normal smartphone use condition.     

AP2M1 Supports TGF-β Signals to Promote Collagen Expression by Inhibiting Caveolin Expression

The extracellular matrix (ECM) is important for normal development and disease states, including inflammation and fibrosis. To understand the complex regulation of ECM, we performed a suppressor screening using Caenorhabditis elegans expressing the mutant ROL-6 collagen protein. One cuticle mutant has a mutation in dpy-23 that encodes the μ2 adaptin (AP2M1) of clathrin-associated protein complex II (AP-2). The subsequent suppressor screening for dpy-23 revealed the lon-2 mutation. LON-2 functions to regulate body size through negative regulation of the tumor growth factor-beta (TGF-β) signaling pathway responsible for ECM production. RNA-seq analysis showed a dominant change in the expression of collagen genes and cuticle components. We noted an increase in the cav-1 gene encoding caveolin-1, which functions in clathrin-independent endocytosis. By knockdown of cav-1, the reduced TGF-β signal was significantly restored in the dpy-23 mutant. In conclusion, the dpy-23 mutation upregulated cav-1 expression in the hypodermis, and increased CAV-1 resulted in a decrease of TβRI. Finally, the reduction of collagen expression including rol-6 by the reduced TGF-β signal influenced the cuticle formation of the dpy-23 mutant. These findings could help us to understand the complex process of ECM regulation in organism development and disease conditions.     

Approaching Ultrastable High‐Rate Li–S Batteries through Hierarchically Porous Titanium Nitride Synthesized by Multiscale Phase Separation

Porous architectures are important in determining the performance of lithium–sulfur batteries (LSBs). Among them, multiscale porous architecutures are highly desired to tackle the limitations of single‐sized porous architectures, and to combine the advantages of different pore scales. Although a few carbonaceous materials with multiscale porosity are employed in LSBs, their nonpolar surface properties cause the severe dissolution of lithium polysulfides (LiPSs). In this context, multiscale porous structure design of noncarbonaceous materials is highly required, but has not been exploited in LSBs yet because of the absence of a facile method to control the multiscale porous inorganic materials. Here, a hierarchically porous titanium nitride (h‐TiN) is reported as a multifunctional sulfur host, integrating the advantages of multiscale porous architectures with intrinsic surface properties of TiN to achieve high‐rate and long‐life LSBs. The macropores accommodate the high amount of sulfur, facilitate the electrolyte penetration and transportation of Li⁺ ions, while the mesopores effectively prevent the LiPS dissolution. TiN strongly adsorbs LiPS, mitigates the shuttle effect, and promotes the redox kinetics. Therefore, h‐TiN/S shows a reversible capacity of 557 mA h g^?1 even after 1000 cycles at 5 C rate with only 0.016% of capacity decay per cycle.