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In this study, we evaluated the antiphotoaging properties of Actinidia chinensis Planch (ACP) and the molecular mechanisms underlying its ability to prevent UVB-mediated photoaging. Administration of the ethanolic extract of ACP (EEACP) to the dorsal area of hairless mice effectively ameliorated UVB-mediated wrinkle formation, epidermal thickening, and loss of lipid droplets in the epidermis. Additionally, the UVB-induced loss of collagen content in the epidermis was significantly attenuated in mouse skin treated with EEACP. The expression of procollagen type 1 and metalloproteinase-1a, which are related to collagen content in the epidermis, was restored by EEACP treatment in UVB-irradiated mice and NIH-3T3 mouse skin fibroblast cells. Interestingly, EEACP effectively ameliorated UVB-induced reactive oxygen species overproduction. Furthermore, the activation/phosphorylation of AKT, rather than mitogen-activated protein kinases, has been identified as a major target of EEACP in preventing UVB-mediated photoaging. Additionally, N-(1 deoxy-1-fructosyl) valine and phenethylamine glucuronide were identified as analytical indicators of EEACP using high-performance liquid chromatography/mass spectrometry. These results suggest that EEACP can be developed as a functional natural agent capable of preventing photoaging by attenuating UVB-induced activation of the reactive oxygen species/AKT pathway.

Staphylococcus aureus is a commensal skin bacterium and a causative agent of infectious diseases. Biofilm formation in S. aureus is a mechanism that facilitates the emergence of resistant strains. This study proposes a mechanism for the regulation of biofilm formation in S. aureus through strain-specific physiological changes induced by the plant steroid diosgenin. A comparison of diosgenin-induced changes in the expression of regulatory genes associated with physiological changes revealed the intracellular regulatory mechanisms involved in biofilm formation. Diosgenin reduced biofilm formation in S. aureus ATCC 6538 and methicillin-resistant S. aureus (MRSA) CCARM 3090 by 39% and 61%, respectively. Conversely, it increased biofilm formation in S. aureus ATCC 29213 and MRSA CCARM 3820 by 186% and 582%, respectively. Cell surface hydrophobicity and extracellular protein and carbohydrate contents changed in a strain-specific manner in response to biofilm formation. An assessment of the changes in gene expression associated with biofilm formation revealed that diosgenin treatment decreased the expression of icaA and spa and increased the expression of RNAIII, agrA, sarA, and sigB in S. aureus ATCC 6538 and MRSA CCARM 3090; however, contrasting gene expression changes were noted in S. aureus ATCC 29213 and MRSA CCARM 3820. These results suggest that a regulatory mechanism of biofilm formation is that activated sigB expression sequentially increases the expression of sarA, agrA, and RNAIII. This increased RNAIII expression decreases the expression of spa, a surface-associated adhesion factor. An additional regulatory mechanism of biofilm formation is that activated sigB expression decreases the expression of an unknown regulator that increases the expression of icaA. This in turn decreases the expression of icaA, which decreases the synthesis of polysaccharide intercellular adhesins and ultimately inhibits biofilm formation. By assessing strain-specific contrasting regulatory signals induced by diosgenin in S. aureus without gene mutation, this study elucidated the signal transduction mechanisms that regulate biofilm formation based on physiological and gene expression changes.

Various poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with the ginger fraction were fabricated by controlling the electrospray parameters and their biocompatibility and antibacterial activity were identified in this study. The morphology of the microspheres was observed using scanning electron microscopy. The core-shell structures of the microparticles and the presence of ginger fraction in the microspheres were confirmed by fluorescence analysis using a confocal laser scanning microscopy system. In addition, the biocompatibility and antibacterial activity of PLGA microspheres loaded with ginger fraction were evaluated through a cytotoxicity test using osteoblast MC3T3-E1 cells and an antibacterial test using Streptococcus mutans and Streptococcus sanguinis, respectively. The optimum PLGA microspheres loaded with ginger fraction were fabricated under electrospray operational conditions with 3% PLGA concentration in solution, an applied voltage of 15.5 kV, a flow rate of 15 µL/min in the shell nozzle, and 3 µL/min in the core nozzle. The effectual antibacterial effect and enhanced biocompatibility were identified when a 3% ginger fraction in PLGA microspheres was loaded.

The gingerols and shogaols derived from ginger have excellent antibacterial properties against oral bacteria. However, some researchers have noted their dose-dependent potential toxicity. The aim of this study was to enhance the biofunctionality and biocompatibility of the application of ginger to dental titanium screws. To increase the amount of coating of the n-hexane-fractionated ginger on the titanium surface and to control its release, ginger was loaded in different concentrations in a photo-crosslinkable GelMA hydrogel. To improve coating stability of the ginger hydrogel (GH), the wettability of the surface was modified by pre-calcification (TNC), then GH was applied on the surface. As a result, the ginger fraction, with a high content of phenolic compounds, was effective in the inhibition of the growth of S. mutans and P. gingivalis. The GH slowly released the main compounds of ginger and showed excellent antibacterial effects with the concentration. Although bone regeneration was slightly reduced with the ginger-loading concentration due to the increased contents of polyphenolic compounds, it was strongly supplemented through the promotion of osteosis formation by the hydrogel and TNC coating. Finally, we proved the biosafety and superior biofunctionalities the GH−TNC coating on a Ti implant. However, it is recommended to use an appropriate concentration, because an excessive concentration of ginger may affect the improved biocompatibility in clinical applications.

Magnesium (Mg), as a biodegradable material, is a promising candidate for orthopedic surgery. Long-bone fractures usually occur in cancellous-bone-rich epiphysis at each end or the cortical-rich diaphysis in the center, with different bone healing processes. Little is known about the differences in results between the two regions when applying Mg implants. Therefore, this study aimed to compare the biodegradation and osteogenesis of Mg implants in a rat model’s epiphysis and diaphysis of the long bone. Twelve male Sprague Dawley rats underwent Mg rod implantation in the distal femoral epiphyses and tibial diaphyses. Every three weeks for up to twelve weeks, degradation behavior, gas evolution, and new bone formation were measured by micro CT. Histomorphology was analyzed by Hematoxylin and Eosin, Villanueva bone staining, and TRAP staining for osteoclastogenesis evaluations. Micro-CT analysis showed statistically significant higher new bone formation in the epiphysis group than in the diaphysis group, which correlated with a lower gas volume. Histological analysis showed higher osseointegration of Mg implants in the epiphyseal region than in the diaphyseal region. The magnesium implant’s osteoclastogenesis-inhibiting properties were shown in the surrounding areas in both the cortical bone of the diaphysis and the cancellous bone of the epiphysis. Our findings show the differences in the magnesium implant’s osteogenesis and biodegradation in the epiphysis and the diaphysis. These dissimilarities indicate a better response of the epiphyseal region to the Mg implants, a promising biomaterial for orthopedic surgery applications.

Growth and maintenance of skeletal muscle is essential for athletic performance and a healthy life. Stimulating the proliferation and differentiation of muscle cells may help prevent loss of muscle mass. To discover effective natural substances enabling to mitigate muscle loss without side effects, we evaluated muscle growth with several compounds extracted from Catalpa bignonioides Walt. Among these compounds, pinoresinol and vanillic acid increased C2C12, a mouse myoblast cell line, proliferation being the most without cytotoxicity. These substances activated the Akt/mammalian target of the rapamycin (mTOR) pathway, which positively regulates the proliferation of muscle cells. In addition, the results of in silico molecular docking study showed that they may bind to the active site of insulin-like growth factor 1 receptor (IGF-1R), which is an upstream of the Akt/mTOR pathway, indicating that both pinoresinol and vanillic acid stimulate myoblast proliferation through direct interaction with IGF-1R. These results suggest that pinoresinol and vanillic acid may be a natural supplement to improve the proliferation of skeletal muscle via IGF-1R/Akt/mTOR signaling and thus strengthen muscles.

Metallic implants (mesh) for guided bone regeneration can result in foreign body reactions with surrounding tissues, infection, and inflammatory reactions caused by micro-organisms in the oral cavity after implantation. This study aimed to reduce the possibility of surgical failure caused by microbial infection by loading antibacterial manuka oil in a biocompatible nanostructure surface on Ti and to induce stable bone regeneration in the bone defect. The manuka oil from New Zealand consisted of a rich β-triketone chemotype, leptospermone, which showed strong inhibitory effects against several bacteria, even at very low oil concentrations. The TiO2 nanotubular layer formed by anodization effectively enhanced the surface hydrophilicity, bioactivity, and fast initial bone regeneration. A concentration of manuka oil in the range of 0.02% to less than 1% can have a synergistic effect on antibacterial activity and excellent biocompatibility. A manuka oil coating (especially with a concentration of 0.5%) on the TiO2 nanotube layer can be expected not only to prevent stenosis of the connective tissue around the mesh and inflammation by microbial infection but also to be effective in stable and rapid bone regeneration.

Tumor angiogenesis is enhanced in all types of tumors to supply oxygen and nutrients for their growth and metastasis. With the development of anti-angiogenic drugs, the importance of technology that closely monitors tumor angiogenesis has also been emerging. However, to date, the technology for observing blood vessels requires specialized skills with expensive equipment, thereby limiting its applicability only to the laboratory setting. Here, we used a preclinical optical imaging system for small animals and, for the first time, observed, in real time, the entire process of blood vessel development in tumor-bearing mice injected with indocyanine green. Time-lapse sequential imaging revealed blood vessel volume and blood flow dynamics on a microscopic scale. Upon analyzing fluorescence dynamics at each stage of tumor progression, vessel volume and blood flow were found to increase as the tumor developed. Conversely, these vascular parameters decreased when the mice were treated with angiogenesis inhibitors, which suggests that the effects of drugs targeting angiogenesis can be rapidly and easily screened. The results of this study may help evaluate the efficacy of angiogenesis-targeting drugs by facilitating the observation of tumor blood vessels easily in a laboratory unit without large and complex equipment.

The present study evaluated the effects of (–)-loliolide isolated from Sargassum horneri (S. horneri) against oxidative stress and inflammation, and its biological mechanism in interferon (IFN)-γ/tumor necrosis factor (TNF)-α-stimulated HaCaT keratinocytes. The results showed that (–)-loliolide improved the cell viability by reducing the production of intracellular reactive oxygen species (ROS) in IFN-γ/TNF-α-stimulated HaCaT keratinocytes. In addition, (–)-loliolide effectively decreased the expression of inflammatory cytokines (interleukin (IL)-4 IL-6, IL-13, IFN-γ and TNF-α) and chemokines (CCL11 (Eotaxin), macrophage-derived chemokine (MDC), regulated on activation, normal T cell expressed and secreted (RANTES), and thymus and activation-regulated chemokine (TARC)), by downregulating the expression of epidermal-derived initial cytokines (IL-25, IL-33 and thymic stromal lymphopoietin (TSLP)). Furthermore, (–)-loliolide suppressed the activation of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling, whereas it activated nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling. Interestingly, the cytoprotective effects of (–)-loliolide against IFN-γ/TNF-α stimulation were significantly blocked upon inhibition of HO-1. Taken together, these results suggest that (–)-loliolide effectively suppressed the oxidative stress and inflammation by activating the Nrf2/HO-1 signaling in IFN-γ/TNF-α-stimulated HaCaT keratinocytes.

Skeletal muscle is an important tissue in energy metabolism and athletic performance. The use of effective synthetic supplements and drugs to promote muscle growth is limited by various side effects. Moreover, their use is prohibited by anti-doping agencies; hence, natural alternatives are needed. Therefore, we evaluated the muscle growth effect of substances that can act like synthetic supplements from edible marine algae. First, we isolated six marine algal polyphenols belonging to the phlorotannin class, namely dieckol (DK), 2,7″-phloroglucinol-6,6′-bieckol (PHB), phlorofucofuroeckol A (PFFA), 6,6′-bieckol (6,6-BK), pyrogallol-phloroglucinol-6,6′-bieckol (PPB), and phloroglucinol (PG) from an edible brown alga, Ecklonia cava and evaluated their effects on C2C12 myoblasts proliferation and differentiation. Of the six phlorotannin isolates evaluated, DK and PHB induced the highest degree of C2C12 myoblast proliferation. In addition, DK and PHB regulates myogenesis by down-regulating the Smad signaling, a negative regulator, and up-regulating the insulin-like growth factor-1 (IGF-1) signaling, a positive regulator. Interestingly, DK and PHB bind strongly to myostatin, which is an inhibitor of myoblast proliferation, while also binding to IGF-1 receptors. Moreover, they bind to IGF-1 receptor. These results suggest that DK and PHB are potential natural muscle building supplements and could be a safer alternative to synthetic drugs.

Chinese chive (Allium tuberosum) is a medicinal food that is cultivated and consumed mainly in Asian countries. Its various phytochemicals and physiological effects have been reported, but only a few phytochemicals are available for skeletal muscle cell proliferation. Herein, we isolated a new compound, kaempferol-3-O-(6″-feruloyl)-sophoroside (1), along with one known flavonoid glycoside (2) and six amino acid (3–8) compounds from the water-soluble fraction of the shoot of the Chinese chive. The isolated compounds were identified using extensive spectroscopic methods, including 1D and 2D NMR, and evaluated for their proliferation activity on skeletal muscle cells. Among the tested compounds, newly isolated flavonoid (1) and 5-aminouridine (7) up-regulated PI3K/Akt/mTOR pathways, which implies a positive effect on skeletal muscle growth and differentiation. In particular, compound 1 down-regulated the Smad pathways, which are negative regulators of skeletal muscle growth. Collectively, we suggest that major constituents of Chinese chive, flavonoids and amino acids, might be used in dietary supplements that aid skeletal muscle growth.

Acute myeloid leukemia (AML) is an aggressive type of human leukemia with a low survival rate, and its complete remission remains challenging. Although chemotherapy is the first-line treatment of AML, it exerts toxicity in noncancerous cells when used in high doses, thus necessitating the development of novel compounds with a high therapeutic window. This study aimed to investigate the anticancer effects of several compounds derived from the fruits of Melia azedarach (a tree with medicinal properties). Among them, 1-cinnamoyltrichilinin (CT) was found to strongly suppress the viability of HL-60 human leukemia cells. CT treatment induced apoptosis and increased nuclear fragmentation and fractional DNA content in HL-60 cells in a dose-dependent manner. CT induced phosphorylation of p38 mitogen-activated protein kinases (p38), though not of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), and activated Bcl-2 family proteins towards the proapoptosis and cleavage of caspase-3 and poly (ADP-ribose) polymerase. Both CT-mediated apoptosis and apoptotic protein expression were reversed by treatment with the p38 inhibitor, thereby indicating the p38 pathway to be critical in CT-stimulated apoptosis. The results collectively indicated CT to suppress HL-60 survival by activating the p38 pathway and inducing apoptosis, hence being a novel potential therapeutic agent for AML.

Inflammation affects various organs of the human body, including skeletal muscle. Phlorotannins are natural biologically active substances found in marine brown algae and exhibit anti-inflammatory activities. In this study, we focused on the effects of phlorotannins on anti-inflammatory activity and skeletal muscle cell proliferation activity to identify the protective effects on the inflammatory myopathy. First, the five species of marine brown algal extracts dramatically inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 cells without toxicity at all the concentrations tested. Moreover, the extracts collected from Ishige okamurae (I. okamurae) significantly increased cell proliferation of C2C12 myoblasts compared to the non-treated cells with non-toxicity. In addition, as a result of finding a potential tumor necrosis factor (TNF)-α inhibitor that regulates the signaling pathway of muscle degradation in I. okamurae-derived natural bioactive compounds, Diphlorethohydroxycarmalol (DPHC) is favorably docked to the TNF-α with the lowest binding energy and docking interaction energy value. Moreover, DPHC down-regulated the mRNA expression level of pro-inflammatory cytokines and suppressed the muscle RING-finger protein (MuRF)-1 and Muscle Atrophy F-box (MAFbx)/Atrgoin-1, which are the key protein muscle atrophy via nuclear factor-κB (NF-κB), and mitogen-activated protein kinase (MAPKs) signaling pathways in TNF-α-stimulated C2C12 myotubes. Therefore, it is expected that DPHC isolated from IO would be developed as a TNF-α inhibitor against inflammatory myopathy.

Guided bone regeneration is a therapeutic method that uses a barrier membrane to provide space available for new bone formation at sites with insufficient bone volume. Magnesium with excellent biocompatibility and mechanical properties has been considered as a promising biodegradable material for guided bone regeneration; however, the rapid degradation rate in the physiological environment is a problem to be solved. In this study, surface modification of pure magnesium mesh was conducted by plasma electrolytic oxidation and hydrothermal treatment to form a densely protective layer on the Mg substrate. The protective layer mainly consisted of Mg(OH)2 with the amorphous calcium phosphate. Then, weight loss measurement and Micro-CT imaging were performed after an immersion test in a simulated body fluid. The effect of surface modification of the magnesium mesh on the guided bone regeneration was evaluated through an in vivo test using the rat calvarial defect model. The biodegradation of the magnesium mesh was identified to be significantly retarded. Additionally, the surface modification of Mg also can improve the bone volume and bone density of calvarial defect in comparison with that of the pristine Mg mesh.

Urban green spaces (UGSs) provide numerous ecosystem services (ESs) that are essential to the well-being of the residents. However, these services are often neglected in regional urban development and spatial planning. This study quantified the ESs of a 10.25 ha UGS at Chungnam National University, Daejeon, Republic of Korea, comprising 27 species with 287 tree individuals, using i-Tree Eco. Key regulating ESs investigated included air pollution removal, carbon storage and sequestration, oxygen production, energy use reduction, avoidance of surface runoff, and replacement and functional values. Results revealed significant annual environmental benefits: 131 kg air pollutants removed (USD 3739.01 or ₩5.16 M), 1.76 Mg carbon sequestered, which is equivalent to 0.18 Mg CO2 ha−1 yr−1 (USD 289.85 or ₩0.40 M), 2.42 Mg oxygen produced, energy savings (including carbon offset) valued at USD 391.29 (₩0.54 M), and 203 m3 reduction in surface runoff (USD 413.09 or ₩0.57 M). The annual total benefits of these urban trees amounted to USD 4833.86 (₩6.67 M), USD 16.83/tree, or USD 0.089/capita. Additionally, these trees had replacement and functional values estimated at USD 311,115.17 (₩429.3 M). The study underscores that species selection and abundance of urban trees are fundamental for maximizing the ES delivery in urban areas, highlighting the role of UGSs in ecological and economical sustainability in cities. These insights are valuable for urban planners and policymakers to optimize benefits of UGSs in cities.

Reduced amounts of collagen and fragmented collagen fibers are characteristics of aging skin. Recently, user-friendly, at-home personal aesthetic devices using light-emitting diode (LED) light have been used for cost-effective and safe skin improvement. However, to dramatically improve the skin via collagen repair, we need to develop an LED-responsive photosensitizer. Corneal collagen crosslinking uses ultraviolet light to activate riboflavin phosphate (RFP) and is used in ophthalmology. RFP is a biocompatible photosensitizer derived from vitamin B2. This study aimed to prove that RFP combined with blue light (BL) can increase collagen crosslinking density, improving its mechanical properties in skin tissue and enhancing skin elasticity. We confirmed the RFP-induced photo-crosslinking in pure collagen by studying changes in its dynamic modulus and matrix morphology using collagen hydrogels. We also measured the changes in the mechanical properties after applying photo-crosslinking on porcine skin. The Young’s modulus (1.07 ± 0.12 MPa) and tensile strength (11.04 ± 1.06 MPa) of the porcine skin after photo-crosslinking were 2.8 and 3.5 times better compared to those of normal porcine skin, respectively. Thus, photo-crosslinking through RFP and BL irradiation can be potentially used for skin improvement using aesthetic LED devices.

Exercise training is a traditional method to maximize remaining function in patients with spinal cord injury (SCI), but the exact mechanism by which exercise promotes recovery after SCI has not been identified; whether exercise truly has a beneficial effect on SCI also remains unclear. Previously, we showed that epigenetic changes in the brain motor cortex occur after SCI and that a treatment leading to epigenetic modulation effectively promotes functional recovery after SCI. We aimed to determine how exercise induces functional improvement in rats subjected to SCI and whether epigenetic changes are engaged in the effects of exercise. A spinal cord contusion model was established in rats, which were then subjected to treadmill exercise for 12 weeks. We found that the size of the lesion cavity and the number of macrophages were decreased more in the exercise group than in the control group after 12 weeks of injury. Immunofluorescence and DNA dot blot analysis revealed that levels of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in the brain motor cortex were increased after exercise. Accordingly, the expression of ten-eleven translocation (Tet) family members (Tet1, Tet2, and Tet3) in the brain motor cortex also elevated. However, no macrophage polarization was induced by exercise. Locomotor function, including Basso, Beattie, and Bresnahan (BBB) and ladder scores, also improved in the exercise group compared to the control group. We concluded that treadmill exercise facilitates functional recovery in rats with SCI, and mechanistically epigenetic changes in the brain motor cortex may contribute to exercise-induced improvements.