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Abstract Twigs of Morus alba have been used in traditional medicine to treat muscle-related symptoms such as aches, numbness, and stiffness. Despite its clinical use in traditional medicine, its active compounds and mode of action have not yet been investigated. Therefore, we aimed to isolate the compounds from the twigs of M. alba and deduce active compounds, key gene targets, and mechanism of action against sarcopenia using network pharmacology analysis. Using various isolation techniques and spectroscopic methods, 43 phytochemicals, including 3 new flavonoids, were isolated and performed network pharmacology analysis. According to the computational-assistant analysis, 28 compounds, 9 genes, and the PI3K-Akt-mTOR signaling pathway were deduced as expected active compounds (EAC), key targets, and the main signaling pathway. To verify the predicted results, the cell proliferation activities of the EAC were evaluated. Especially, moracin E and M significantly increased by 130% (p

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.

For primary prevention, it is important for public health and clinical medicine to identify and characterize modifiable risk factors of stroke. In existing literature, the impact of occupational variables on ischemic and hemorrhagic stroke has been extensively studied. This review summarizes the available data on the significance of occupational variables in stroke. The results of this review suggest that there is sufficient evidence for the relationship between increased risk of stroke and job stress, working in extreme temperatures, long working hours, and/or shift work. The association between long working hours and occupational exposure to noise and chemicals remains inconclusive although several studies have reported this finding. This review will act as a step toward future research and provide information that may serve as a baseline for developing targeted interventions to prevent stroke in the working population.

Front-of-package (FOP) is one of the most direct communication channels connecting manufacturers and consumers, as it displays crucial information such as certification, nutrition, and health. Traditional methods for obtaining information from FOPs often involved manual collection and analysis. To overcome these labor-intensive characteristics, new methods using two artificial intelligence (AI) approaches were applied for information monitoring of FOPs. In order to provide practical implementations, a case study was conducted on infant food products. First, FOP images were collected from Amazon.com. Then, from the FOP images, 1) the certification usage status of the infant food group was obtained by recognizing the certification marks using object detection. Moreover, 2) the nutrition and health-related texts written on the images were automatically extracted based on optical character recognition (OCR), and the associations between health-related texts were identified by network analysis. The model attained a 94.9% accuracy in identifying certification marks, unveiling prevalent certifications like Kosher. Frequency and network analysis revealed common nutrients and health associations, providing valuable insights into consumer perception. These methods enable fast and efficient monitoring capabilities, which can significantly benefit various food industries. Moreover, the AI-based approaches used in the study are believed to offer insights for related industries regarding the swift transformations in product information status.

The Korea Strait (KS) is a crucial marine passage for transporting heat, salt, and materials from the South Sea to the East Sea. The Tsushima Warm Water (TWW) and Korea Strait Bottom Cold Water (KSBCW) are major water masses that flow across the strait, but their effects on prokaryotic communities have been unclear. We used high-throughput sequencing to study the impact of TWW and KSBCW on prokaryotic composition and metabolic changes in the upper (0–50m; UL), middle (50–75m; ML), and bottom (75–150m; BL) layers during the fall of 2018 and 2019. The results showed that the UL had a freshwater influence from Changjiang Diluted Water in 2019, altering prokaryotic compositions and metabolic potentials. The KSBCW in the BL transported new bacterial communities with unique metabolic characteristics. Key genes involved in carbon metabolism had water mass impacts, preferring lower saline and temperature environments, and carbon fixation potential shifted from phototrophs in 2018 to chemotrophs in 2019. Temperature changes induced acclimation processes producing heat- and cold-shock genes/proteins. Our findings indicate that the freshwater influence and KSBCW modified the prokaryotic composition and metabolic function differentially. These results are important in understanding the relationship between water masses and ongoing environmental changes in this understudied region.

Objectives: Polystyrene is a plastic that leads to environmental pollution. In particular, expanded polystyrene is very light and takes up much space, causing additional environmental problems. The aim of this study was to isolate new symbiotic bacteria which degraded polystyrene from mealworms. Methods: The population of polystyrene degrading bacteria was increased by enrichment culture of intestinal bacteria from mealworms with polystyrene as a sole carbon source. The degradation activity of isolated bacteria was evaluated by morphological change of micro-polystyrene particles and the surface change of polystyrene films. Results: Eight isolated species (Acinetobacter septicus, Agrobacterium tumefaciens, Klebsiella grimontii, Pseudomonas multiresinivorans, Pseudomonas nitroreducens, Pseudomonas plecoglossicida, Serratia marcescens, and Yokenella regensburgei) were identified that degrade polystyrene. Conclusion: Bacterial identification shows that a broad spectrum of bacteria decomposing polystyrene coexists in the intestinal tract of mealworms.

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.

ObjectiveThe aim of this study was to evaluate the comparative effectiveness of a low-calorie diet (LCD) combined with acupuncture, cognitive behavioral therapy (CBT), meal replacements (MR), and exercise on weight loss.MethodsThe electronic databases MEDLINE, EMBASE, CENTRAL, CNKI, RISS, and KISS were searched systematically. Randomized controlled trials (RCTs) that directly compared the effect of a low-calorie diet (LCD)-combined acupuncture, CBT, and exercise and an MR-based diet on weight loss with LCD-alone for adults with simple obesity (body mass index [BMI] > 25) published before August 2021 were included in the study. Two investigators extracted and coded the data using a template. Any disagreements between investigators were resolved through discussion. Changes in BMI or weight were transformed to Hedges’ g values with a 95% CI, and network meta-analyses using a Bayesian random-effects model were conducted.ResultsA total of thirty-two trials involving 3,364 patients were finally included in the study. The effect sizes of four interventions were medium, in the order of acupuncture (Hedges’ g = 0.48, 95% CI = 0.25 - 0.71), CBT (Hedges’ g = 0.42, 95% CI = 0.20 - 0.63), MR (Hedges’ g = 0.32, 95% CI = 0.19 - 0.45), and exercise (Hedges’ g = 0.27, 95% CI = 0.06 - 0.46).In terms of intervention period, acupuncture was effective in the short period (≤ 12 weeks, Hedges’ g = 0.39, 95% CI = 0.12 - 0.67) and the long period (>12 weeks, Hedges’ g = 0.89, 95% CI = 0.37 - 1.40), whereas CBT (Hedges’ g = 0.51, 95% CI = 0.26 - 0.76) and exercise (Hedges’ g = 0.37, 95% CI = 0.12 - 0.59) were effective only in the long period. MR was effective only in the short period (Hedges’ g = 0.35, 95% CI = 0.18 - 0.53).ConclusionsThis study suggests that acupuncture, CBT, MR, and exercise for simple obesity show a medium effect size, and their effectiveness differs according to the intervention period.

Abstract The present study aimed to evaluate the protective effect of a methanol extract of Sargassum horneri (SHM), which contains 6-hydroxy-4,4,7a-trimethyl-5,6,7,7a-tetrahydrobenzofuran-2(4H)-one (HTT) and apo-9′-fucoxanthinone, against ultraviolet B (UVB)-induced cellular damage in human keratinocytes and its underlying mechanism. SHM significantly improved cell viability of UVB-exposed human keratinocytes by reducing the generation of intracellular reactive oxygen species (ROS). Moreover, SHM inhibited UVB exposure-induced apoptosis by reducing the formation of apoptotic bodies and the populations of the sub-G1 hypodiploid cells and the early apoptotic cells by modulating the expression of the anti- and pro-apoptotic molecules, Bcl-2 and Bax, respectively. Furthermore, SHM inhibited NF-κB p65 activation by inducing the activation of Nrf2/HO-1 signaling. The cytoprotective and antiapoptotic activities of SHM are abolished by the inhibition of HO-1 signaling. In further study, SHM restored the skin dryness and skin barrier disruption in UVB-exposed human keratinocytes. Based to these results, our study suggests that SHM protects the cells against UVB-induced cellular damages through the Nrf2/HO-1/NF-κB p65 signaling pathway and may be potentially useful for the prevention of UVB-induced skin damage.

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.

Objective: To investigate the anti-senescence effect of 3-bromo-4,5- dihydroxybenzaldehyde (BDB) from Polysiphonia morrowii Harvey in human dermal fibroblasts (HDF). Methods: HDF were subjected to treatment of BDB and then treated with hydrogen peroxide (H2O2) to induce premature senescence. Senescence-associated β-galactosidase (SA-β-gal) activity in HDF was determined using the SA-β-gal staining method. Intracellular reactive oxygen species (ROS) production was measured using the 2’,7’-dichlorodihydrofluorescein diacetate assay. Western blotting assay was performed to assess the level of antioxidant enzyme glutathione peroxidase 1 (GPX1). In addition, intracellular collagen and collagenase contents were analyzed using the respective ELISA kits. Elastase activity in HDF supernatants was measured from p-nitroaniline release and normalized using total protein content. Results: Treatment of HDF with H2O2 increased the activity of SAP-gal, but BDB pre-treatment resulted in the reduction of SA-β- gal activity. Moreover, BDB significantly reduced H2O2-induced intracellular ROS production. BDB also markedly increased the level of GPX1, which was inhibited by 400 µM of H2O2. Furthermore, in in vitro study, BDB significantly increased intracellular collagen content and decreased matrix metalloproteinase-1 and elastase activities in HDF. Conclusions: Our results demonstrate that BDB shows anti- senescence and anti-wrinkle activities in vitro.

Obese sarcopenia is associated with palmitic acid (PA), an abundant circulating saturated fatty acid. This study examined a non-cytotoxic concentration of PA to provide mechanistic insights into PA-impaired skeletal myogenesis and potential medicinal and dietary interventions through edible brown seaweed, Ishige okamurae (IO). C2C12 cells were examined for myogenic markers, adipogenic factors, and regenerative capacity through growth regulators against PA interference to assess IO and purified diphloroethohydoxycarmalol (DPHC) as potential treatments. Both IO and DPHC improved myogenic marker (myogenin, MyoD, and MyHC) levels. PA down-regulated myogenic markers while improving adipogenic factors (PPARγ, c/EBPα, A-FABP), DPHC significantly arbitrated the negative effects. DPHC treatment also improved phosphorylation of the growth regulatory PI3K/Akt/mTOR axis over the adverse effects of PA. The results of this study suggested regulatory mechanisms through which the bioactive components IO and DPHC based on the sustainable utilization of I. okamurae inhibited the PA-induced impairment of skeletal myogenesis.

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.

Obesity is known as metabolic syndrome and it affects many tissues including adipose tissue, liver, and central nervous system (CVS). Gambi-jung (GBJ) is a modified prescription of Taeumjowi-tang (TJT), which has been used to treat obesity in Korea. GBJ is composed of 90% Ephedra sinica Stapf (ES). Therefore, the present study was designed to assess the antiobesity effects of GBJ and to compare the effects of GBJ and ES on obesity. GBJ administration remarkably reduced the body weight, Body mass index (BMI), and body fat percentage compared to the ES administration in human subjects. GBJ-treated mice had lower white adipose tissue (WAT) amounts than ES-treated mice. GBJ and ES administration enhanced adenosine monophosphate-activated protein kinase (AMPK) expression in 3T3-L1 adipocytes, epididymal WAT and liver of HFD-induced obese mice. Moreover, GBJ and ES reduced food intake by suppressing the mRNA levels of orexigenic peptides, agouti-related protein (AgRP) and neuropeptide-Y (NPY), as well as AMPK in the brain of HFD-induced obese mice. Furthermore, GBJ-treated mice had dramatically lower expression of macrophage marker F4/80 in epididymal WAT than those of ES-treated mice. Based on these results, we suggest the use of GBJ as a natural drug to control weight gain.

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.

Abstract Background This study is aimed at identifying the anti-inflammatory properties of 70% ethanol extract produced from an edible brown seaweed Sargassum horneri (SJB-SHE) with industrial-scale production by Seojin Biotech Co. Ltd. S. horneri is a rich source of nutrient and abundantly growing along the shores of Jeju, South Korea. Methods Here, we investigated the effect of SJB-SHE on LPS-activated RAW 264.7 macrophages. The cytotoxicity and NO production of SJB-SHE were evaluated using MTT and Griess assays, respectively. Additionally, protein expression and gene expression levels were quantified using ELISA, Western blots, and RT-qPCR. Results Our results indicated that pre-treatment of RAW 264.7 macrophages with SJB-SHE significantly inhibited LPS-induced NO and PGE2 production. SJB-SHE downregulated the proteins and genes expression of LPS-induced iNOS and COX2. Additionally, SJB-SHE downregulated LPS-induced production of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-6, and IL-1β). Furthermore, SJB-SHE inhibited nuclear factor kappa-B (NF-κB) activation and translocation to the nucleus. SJB-SHE also suppressed the phosphorylation of mitogen-activated protein kinases (ERK1/2 and JNK). Conclusions Collectively, our results demonstrated that SJB-SHE has a potential anti-inflammatory property to use as a functional food ingredient in the future.

Big belly seahorse (Hippocampus abdominalis) is a well-known marine organism recognized for its pharmacological value. In this study, peptides derived from natively (Jeju-do, Republic of Korea) farmed seahorses were investigated for their potency on myoblast differentiation and endurance capacitance. Cell viability studies on C2C12 mouse myoblast cells showed that more than 80% of the cells treated with peptides were metabolically active. Morphological observation illustrated the loss of characteristic radial branching towards elongated and well-developed muscle fibers in the peptide-treated C2C12 cells. Immunoblot study on the in vitro translational expression level of key myogenic regulatory proteins (MyoD, MyoG, MyHC) and an in vivo endurance study (using zebrafish as a working model) demonstrated the significance of peptides on the myogenesis process and endurance swimming performance against water flow and gradient, respectively. Collectively, our findings suggest that seahorse-derived peptides can be used as a therapeutic nutrient supplement for improved endurance.

Brown algae are known to contain rich anti-inflammatory compounds. The objective of this study was to identify anti-inflammatory compound in the Sargassum macrocarpum and anti-inflammatory effect of tuberatolide B (TTB) was investigated. TTB significantly suppressed the production of NO and pro-inflammatory cytokines such as interleukin (IL)-6 and IL-1β. In addition, the mechanism involved in the inhibition of the inflammatory effect of LPS by TTB was investigated. The results showed that TTB aforementioned this effect through NF-κB and MAPKs phosphorylation pathways. We also assessed the anti-inflammatory activity of TTB using in vivo zebrafish model. In LPS-stimulated zebrafish, TTB enhanced survival and significantly inhibited the NO production and mRNA expression of inducible NO synthase. Therefore, anti-inflammatory activity of TTB against LPS in RAW264.7 cells and the zebrafish model was determined. These finding suggest that TTB may be used as functional anti-inflammatory foods and nutraceuticals.

Magnesium alloys are biodegradable metals receiving increasing attention, but the clinical applications of these materials are delayed by concerns over the rapid corrosion rate and gas formation. Unlike corrosion, which weakens mechanical properties, the gas formation issue has received little attention. Therefore, we evaluated the gas formation and biological effects for Mg implants through preclinical (immersed in Earle’s balanced salt solution and in vivo) and clinical studies. The immersion test examined the gas volume and composition. The in vivo study also examined gas volume and histological analysis. The clinical study examined the gas volume and safety after Mg screw metatarsal fixation. Gas was mainly composed of H2, CO and CO2. Maximum volumes of gas formed after 5 days for in vivo and 7 days in clinical study. Within the clinical examination, two superficial wound complications healed with local wound care. Osteolytic lesions in the surrounding metaphysis of the Mg screw insertion developed in all cases and union occurred at 3 months. Mg implants released gas with variable volumes and composition (H2, CO, and CO2), with no long-term toxic effects on the surrounding tissue. The implants enabled bone healing, although complications of wound breakdown and osteolytic lesions developed.

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.

Pinus thunbergii is a black pine that has been widely used in health-promoting foods. This study was conducted to investigate the hepatoprotective effects of the alcohol-aqueous extract of Pinus thunbergii PARL leaves (PTE) in ethanol-induced liver-damaged mice. PTE increased the weight and survival rate of mice while reducing the levels of serum hepatic marker enzymes. PTE also restored the levels of antioxidant enzymes in liver tissues while drastically increasing lipid peroxidation concentrations. Histopathological examination of PTE-treated mice presented relatively less lipid droplets and hepatic tissue damage compared to ethanol-treated mice. Finally, to identify PTE components, Natural Products Application Solution with UNIFI along with an in-house library was processed and results revealed 35 compounds in the extract. These compounds were reported to exhibit significant antioxidant and/or hepatoprotective properties. Our results suggest that PTE improves liver function and can be developed as a food product with hepatoprotective effects.

Objective To investigate whether fracture type, surgical procedure, or fracture grade affect knee pain during postoperative rehabilitation after a hip fracture. Methods We conducted a retrospective case-controlled study of 139 patients during postoperative rehabilitation after surgery for hip fractures. Patients were divided into two groups: patients experiencing knee pain during the first week of postoperative rehabilitation, and patients without knee pain. We compared the types of fracture, surgical procedure, and fracture grade between the two groups. Results We enrolled 52 patients (37.4%) with knee pain during the first weeks of postoperative rehabilitation. For type of fracture, knee pain was more common with intertrochanteric fracture than with femur neck fracture (48.8% vs. 21.1%, respectively; p=0.001). For the surgical procedure, there was no significant difference between the groups. For the fracture grade, the grades classified as unstable fractures were more common in the group of intertrochanteric fracture patients with knee pain than in those without knee pain (74.1% vs. 36.4%, respectively; p=0.002). Conclusion Intertrochanteric fracture affected knee pain after hip fracture surgery more than did femur neck fracture, particularly in unstable fractures. Furthermore, there was no difference in each fracture type according to the surgical procedure. Careful examination and management for knee pain is needed in patients with hip fracture surgery.

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.

Abstract In this study, a two-step surface treatment was developed to restrain the rapid primary degradation of a biodegradable Mg alloy and to improve their biocompatibility. Micro arc oxidation (MAO) coating was performed in alkaline electrolytes such as 1.0 M NaOH with 0.1 M glycerol and 0.1 M Na3PO4. Hydrothermal treatment was performed in 0.1 M Ca-EDTA (C10H12CaN2Na2O8) and 0.5 M NaOH solution at 90 °C for different times (6, 12, 24, and 48 h). The film morphology and chemical properties were evaluated by XRD and FE-SEM. The electrochemical and corrosion behaviors were examined in the simulated body fluid, and cytotoxicity was assessed using MC3T3-E1 cells. After MAO coating, an oxide layer containing $${\bf{P}}{{\bf{O}}}_{4}^{3-}$$ P O 4 3 − formed on the surface. During the hydrothermal treatment in Ca-EDTA solution, calcium phosphate and Mg(OH)2 were produced via a reaction between $${\bf{P}}{{\bf{O}}}_{4}^{3-}$$ P O 4 3 − on the surface and Ca2+ in solution. The layer with ceramics and oxides was grown on the surface with increasing hydrothermal treatment time, and improved the surface corrosion resistance. The 24 h hydrothermal-treated group showed the lowest immersion corrosion rate and high cell viability. Therefore, this treatment was the most favorable surface modification for improving the initial corrosion resistance and bioactivity of the biodegradable Mg alloy.

Abstract Seahorse, a syngnathidae fish, is one of the important organisms used in Chinese traditional medicine. Hippocampus abdominalis, a seahorse species successfully cultured in Korea, was validated for use in food by the Ministry of Food and Drug Safety in February 2016; however. the validation was restricted to 50% of the entire composition. Therefore, to use H. abdominalis as a food ingredient, H. abdominalis has to be prepared as a mixture by adding other materials. In this study, the effect of H. abdominalis on muscles was investigated to scientifically verify its potential bioactivity. In addition, the anti-fatigue activity of a mixture comprising H. abdominalis and red ginseng (RG) was evaluated to commercially utilize H. abdominalis in food industry. H. abdominalis was hydrolyzed using Alcalase, a protease, and the effect of H. abdominalis hydrolysate (HH) on the muscles was assessed in C2C12 myoblasts by measuring cell proliferation and glycogen content. In addition, the mixtures comprising HH and RG were prepared at different percentages of RG to HH (20, 30, 40, 50, 60, 70, and 80% RG), and the anti-fatigue activity of these mixtures against oxidative stress was assessed in C2C12 myoblasts. In C2C12 myoblasts, H2O2-induced oxidative stress caused a decrease in viability and physical fatigue-related biomarkers such as glycogen and ATP contents. However, treatment with RG and HH mixtures increased cell viability and the content of fatigue-related biomarkers. In particular, the 80% RG mixture showed an optimum effect on cell viability and ATP synthesis activity. In this study, all results indicated that HH had anti-fatigue activity at concentrations approved for use in food by the law in Korea. Especially, an 80% RG to HH mixture can be used in food for ameliorating fatigue.

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.

Background Vertical reduction mammaplasty has been criticized for its inability to address larger cases of mammary hypertrophy, with a relatively high frequency of sensory loss reported. This article describes our single-institution experience with modified vertical reduction mammaplasty for varying degrees of breast reduction. Methods Thirty-three patients underwent breast reduction using the modified vertical reduction mammaplasty technique with a superomedial dermoglandular pedicle and modifications involving breast parenchyma excision. The degree of sensory preservation in the nipple-areola complex (NAC) was compared with preoperative sensation using an ordinal scale (0, insensate; 10, unchanged). Postoperative outcomes were evaluated through a photogrammetric analysis. Satisfaction with postoperative outcomes was assessed using a telephone questionnaire survey (1, very poor; 5, very good). Results The modified vertical mammaplasty technique allowed for reductions of up to 1,800 g per side. The mean resection weight was 459.24 g per breast (range, 76-1,800 g). Of the 59 operations, 9 involved complications without significant morbidity. The sensibility of the NAC recovered in most patients by 5 months after the operation. The mean satisfaction score was 3.4, which was between 'no change' and 'satisfied.' Conclusions Modified vertical reduction mammaplasty allows a single surgeon to address varying degrees of breast hypertrophy.

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.

The HOG (High Osmolarity Glycerol response) pathway plays a central role in controlling stress response, ergosterol biosynthesis, virulence factor production, and differentiation of Cryptococcus neoformans, which causes fatal fungal meningoencephalitis. Recent transcriptome analysis of the HOG pathway discovered a Hog1-regulated gene (CNAG_00130.2), encoding a putative protein kinase orthologous to Rck1/2 in Saccharomyces cerevisiae and Srk1 in Schizosaccharomyces pombe. Its function is not known in C. neoformans. The present study functionally characterized the role of Hrk1 in C. neoformans. Northern blot analysis confirmed that HRK1 expression depends on the Hog1 MAPK. Similar to the hog1Δ mutant, the hrk1Δ mutant exhibited almost complete resistance to fludioxonil, which triggers glycerol biosynthesis via the HOG pathway. Supporting this, the hrk1Δ mutant showed reduced intracellular glycerol accumulation and swollen cell morphology in response to fludioxonil, further suggesting that Hrk1 works downstream of the HOG pathway. However, Hrk1 also appeared to have Hog1-independent functions. Mutation of HRK1 not only further increased osmosensitivity of the hog1Δ mutant, but also suppressed increased azole-resistance of the hog1Δ mutant in an Erg11-independent manner. Furthermore, unlike the hog1Δ mutant, Hrk1 was not involved in capsule biosynthesis. Hrk1 was slightly involved in melanin production but dispensable for virulence of C. neoformans. These findings suggest that Hrk1 plays both Hog1-dependent and -independent roles in stress and antifungal drug susceptibility and virulence factor production in C. neoformans. Particularly, the finding that inhibition of Hrk1 substantially increases azole drug susceptibility provides a novel strategy for combination antifungal therapy.