Identification of Peucedanum japonicum Thunb. extract components and their protective effects against dexamethasone-induced muscle atrophy.

BACKGROUND: Peucedanum japonicum Thunb. (PJ) is a vegetable widely consumed in East Asia and is known to have anticancer and anti-inflammatory effects. However, the effect of PJ on muscle atrophy remains elusive. PURPOSE: This study aimed to investigate the effect of PJ and its active compound on dexamethasone (DEX)-induced muscle atrophy. METHODS: We performed qualitative and quantitative analysis of PJ using ultra-performance liquid chromatography-mass spectrometry tandem mass spectrometry (UPLC-MS/MS) and high-performance liquid chromatography (HPLC), respectively. The efficacy of PJ and its main compound 4-caffeoylquinic acid (CQA) on muscle atrophy was evaluated in DEX-induced myotube atrophy and DEX-induced muscle atrophy in mouse myoblasts (C2C12) and C57BL/6 mice, in vitro and in vivo, respectively. RESULTS: The UPLC-MS/MS and HPLC data showed that the concentration of 4-CQA in PJ was 18.845 mg/g. PJ and 4-CQA treatments significantly inhibited DEX-induced myotube atrophy by decreasing protein synthesis and glucocorticoid translocation to the nucleus in C2C12 myotubes. In addition, PJ enhanced myogenesis by upregulating myogenin and myogenic differentiation 1 in C2C12 cells. PJ supplementation effectively increased muscle function and mass, downregulated atrogenes, and decreased proteasome activity in C57BL/6 mice. Additionally, PJ effectively decreased the nuclear translocation of forkhead transcription factor 3 alpha by inhibiting glucocorticoid receptor. CONCLUSION: Overall, PJ and its active compound 4-CQA alleviated skeletal muscle atrophy by inhibiting protein degradation. Hence, our findings present PJ as a potential novel pharmaceutical candidate for the treatment of muscle atrophy.

Gromwell (Lithospermum erythrorhizon) Attenuates High-Fat-Induced Skeletal Muscle Wasting by Increasing Protein Synthesis and Mitochondrial Biogenesis.

Gromwell (Lithospermum erythrorhizon, LE) can mitigate obesity-induced skeletal muscle atrophy in C2C12 myotubes and high-fat diet (HFD)-induced obese mice. The purpose of this study was to investigate the anti-skeletal muscle atrophy effects of LE and the underlying molecular mechanism. C2C12 myotubes were pretreated with LE or shikonin, and active component of LE, for 24 h and then treated with 500 µM palmitic acid (PA) for an additional 24 h. Additionally, mice were fed a HFD for 8 weeks to induced obesity, and then fed either the same diet or a version containing 0.25% LE for 10 weeks. LE attenuated PA-induced myotubes atrophy in differentiated C2C12 myotubes. The supplementation of LE to obese mice significantly increased skeletal muscle weight, lean body mass, muscle strength, and exercise performance compared with those in the HFD group. LE supplementation not only suppressed obesity-induced skeletal muscle lipid accumulation, but also downregulated TNF-α and atrophic genes. LE increased protein synthesis in the skeletal muscle via the mTOR pathway. We observed LE induced increase of mitochondrial biogenesis and upregulation of oxidative phosphorylation related genes in the skeletal muscles. Furthermore, LE increased the expression of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha and the phosphorylation of adenosine monophosphate-activated protein kinase. Collectively, LE may be useful in ameliorating the detrimental effects of obesity-induced skeletal muscle atrophy through the increase of protein synthesis and mitochondrial biogenesis of skeletal muscle.

Effects of Music-Based Interventions on Motor and Non-Motor Symptoms in Patients with Parkinson's Disease: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis examined previous studies on music-based interventions for individuals with Parkinson's disease (PD). The effectiveness of the interventions on various motor and non-motor outcomes was evaluated. This review was conducted by searching PubMed, CINAHL, PsycINFO, and Cochrane Library CENTRAL prior to June 2022 for randomized controlled trial (RCT) and controlled clinical trial (CCT) studies published in English. Data were expressed as weighted/standardized mean difference (MD/SMD) with 95% confidence intervals (CI). I2 index was used for heterogeneity. The initial search identified 745 studies, and 13 studies involving 417 participants with PD which met the inclusion criteria included in this review. The results of the meta-analysis revealed that music-based interventions can significantly improve walking velocity (MD = 0.12, 95% CI = 0.07~0.16, p < 0.00001), stride length (MD = 0.04, 95% CI = 0.02~0.07, p = 0.002), and mobility (MD = −1.05, 95% CI = −1.53~−0.57, p < 0.0001). However, the results did not support significant effects for music-based interventions on cadence (MD = 3.21, 95% CI = −4.15~10.57, p = 0.39), cognitive flexibility (MD = 20.91, 95% CI = −10.62~52.44, p = 0.19), inhibition (SMD = 0.07, 95% CI = −0.40~0.55, p = 0.76), and quality of life (SMD = −0.68, 95% CI= −1.68~0.32, p = 0.18). The findings suggest that music-based interventions are effective for the improvement of some motor symptoms, but evidence for non-motor symptoms is limited. Further high-quality studies with a larger sample size are required to obtain the robust effects of music-based interventions on various outcomes among patients with PD.

Friend-shield protection from the crowd: How friendship makes people feel invulnerable to COVID-19.

When deciding whether to eat inside a restaurant or how many health protection items to purchase, individuals in the coronavirus disease (COVID-19) era tend to consider the infection risk of crowds of generalized others. With a field study and four experiments, the present study identifies associations between COVID-19 and friendship (e.g., thinking of a friend while reading COVID-19-related news, perceiving a friend as the source of infection, noting friends' presence during potential COVID-19 exposure) that decrease both infection risk perceptions and protective behaviors. The sense of safety that stems from psychological closeness of friends reduces perceived virus infection risks associated with third-party crowds. The distinction between psychological closeness and safety toward friends versus acquaintances widens with clear in-group/out-group boundaries, such that this friend-shield effect is especially pronounced among people whose group boundaries are well established. Limiting interactions to close friends and family members is a common protective measure to reduce COVID-19 transmission risk, but the study findings demonstrate that this practice also unintentionally creates other issues, in that people tend to perceive reduced health risks and engage in potentially hazardous health behaviors. By identifying this risk and encouraging more holistic responses, this research offers implications for individuals, health officials, and policymakers. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Synergistic effect of Mahaenggamseok-tang in the treatment of pediatric patients with lower respiratory tract infections: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Infants are often hospitalized because of lower respiratory tract infections, and overuse of antibiotics to treat such infections has led to severe problems. Herbal medicines may be more effective and safer than antibiotics. Mahaenggamseok-tang is a common herbal medicine in Asia, but the evidence for its effectiveness in lower respiratory tract infection treatment is insufficient. This review assesses the efficacy of Mahaenggamseok-tang in treating lower respiratory tract infections. METHODS: The study used Chinese, English, and Korean databases, as well as one Japanese database. All included studies were randomized controlled trials comparing Mahaenggamseok-tang with medication to treat lower respiratory tract infections. Studies using Mahaenggamseok-tang plus Western medicine were also included. Standardized mean difference (SMD), risk ratio (RR) with 95% confidence interval (CI), and risk of bias were analyzed using Review Manager 5.4 software. The GRADEpro website was used to assess the reviews. RESULTS: Seventeen randomized controlled trials with a total of 1993 participants were included in the meta-analysis. All studies compared the Mahaenggamseok-tang plus Western medicine group to the Western medicine only group. Meta-analysis showed that Mahaenggamseok-tang affected total effective rate (risk ratio: 1.20, 95% confidence interval [CI]: 1.10-1.31, P < .001), cough disappearance time (SMD: -1.62, 95% CI: -2.30 to -0.95, P < .001), fever disappearance time (SMD: -2.04, 95% CI: -2.87 to -1.21, P < .001), abnormal lung sound disappearance time (SMD: -1.68, 95% CI: -2.43 to -0.93, P < .001), Creactive protein (SMD: -3.18, 95% CI: -4.36 to -1.99, P < .001), procalcitonin (SMD: -5.04, 95% CI: -9.20 to -0.88, P < .05), tumor necrosis factor-α (SMD: -0.84, 95% CI: -1.46 to -0.23, P < .01), IgE (SMD: -2.69, 95% CI: -2.91 to -2.47, P < .001), and adverse events (risk ratio: 0.44, 95% CI: 0.29-0.68, P < .001), but not interleukin-6 (SMD: -1.59, 95% CI: -3.48 to 0.30, P>.05). DISCUSSION: Mahaenggamseok-tang plus Western medicine is more effective and safer than Western medicine alone for treating lower respiratory tract infections. However, the included randomized controlled trials were not randomized well; therefore, better randomized randomized controlled trials are needed to make significant recommendations.PROSPERO registration number: CRD42020165698.

Dracunculin Inhibits Adipogenesis in Human Bone Marrow-Derived Mesenchymal Stromal Cells by Activating AMPK and Wnt/ß-Catenin Signaling.

Increased bone marrow adiposity is widely observed in patients with obesity and osteoporosis and reported to have deleterious effects on bone formation. Dracunculin (DCC) is a coumarin isolated from Artemisia spp. but, until now, has not been studied for its bioactive potential except antitrypanosomal activity. In this context, current study has reported the anti-adipogenic effect of DCC in human bone marrow-derived mesenchymal stromal cells (hBM-MSCs). DCC dose-dependently inhibited the lipid accumulation and expression of adipogenic transcription factors peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα) in hBM-MSCs induced to undergo adipogenesis. To elucidate its action mechanism, the effect of DCC on Wnt/ß-catenin and AMPK pathways was examined. Results showed that DCC treatment activated Wnt/ß-catenin signaling pathway via AMPK evidenced by increased levels of AMPK phosphorylation and Wnt10b expression after DCC treatment. In addition, DCC treated adipo-induced hBM-MSCs exhibited significantly increased nuclear levels of ß-catenin compared with diminished nuclear PPARγ levels. In conclusion, DCC was shown to be able to hinder adipogenesis by activating the ß-catenin via AMPK, providing potential utilization of DCC as a nutraceutical against bone marrow adiposity.

Antioxidant Activity of Valeriana fauriei Protects against Dexamethasone-Induced Muscle Atrophy.

Skeletal muscle atrophy is defined as wasting or loss of muscle. Although glucocorticoids (GCs) are well-known anti-inflammatory drugs, their long-term or high-dose use induces skeletal muscle atrophy. Valeriana fauriei (VF) is used to treat restlessness, anxiety, and sleep disorders; however, its effects on skeletal muscle health have not been investigated. This study investigated whether Valeriana fauriei could ameliorate muscle atrophy. We induced muscle atrophy in vitro and in vivo, by treatment with dexamethasone (DEX), a synthetic GC. In DEX-induced myotube atrophy, Valeriana fauriei treatment increased the fusion index and decreased the expression of muscle atrophic genes such as muscle atrophy F-box (MAFbx/Atrogin-1) and muscle RING-finger protein 1 (MuRF1). In DEX-treated mice with muscle atrophy, Valeriana fauriei supplementation increased the ability to exercise, muscle weight, and cross-sectional area, whereas it inhibited myosin heavy chain isoform transition and the expression of muscle atrophy biomarkers. Valeriana fauriei treatment led to via the downregulation of muscle atrophic genes via inhibition of GC receptor translocation. Valeriana fauriei was also found to act as a reactive oxygen species (ROS) scavenger. Didrovaltrate (DI), an iridoid compound from Valeriana fauriei, was found to downregulate atrophic genes and decrease ROS in the DEX-induced myotube atrophy. Consolidated, our results indicate that Valeriana fauriei prevents DEX-induced muscle atrophy by inhibiting GC receptor translocation. Further, Valeriana fauriei acts as a ROS scavenger, and its functional compound is didrovaltrate. We suggest that Valeriana fauriei and its functional compound didrovaltrate possess therapeutic potentials against muscle atrophy.

Risk of upper gastrointestinal bleeding in patients on oral anticoagulant and proton pump inhibitor co-therapy.

BACKGROUND: Proton pump inhibitors (PPIs) are known to reduce the risk of upper gastrointestinal bleeding in patients on oral anticoagulants, and patients are increasingly on oral anticoagulants and PPI co-therapy. However, evidence is lacking on the safety and effectiveness of oral anticoagulants when co-administered with PPIs. METHODS: Among patients initiating oral anticoagulants (warfarin and non-vitamin K antagonist oral anticoagulants [NOACs], i.e. rivaroxaban, dabigatran, apixaban, and edoxaban) during 2013-2017, those concomitantly prescribed PPIs were identified (n = 19,851). The primary endpoint was hospitalization for major upper gastrointestinal bleeding, and secondary endpoints were death and ischemic stroke. RESULTS: During a mean 1.4 years of follow-up, the primary endpoint occurred in 512 (2.58%) patients. Overall, NOACs were associated with lower upper gastrointestinal bleeding risk after adjustment for age, sex, comorbidities and concomitant medications (adjusted hazard ratio 0.78, 95% confidence interval 0.65-0.94), compared to warfarin. There was no significant difference in upper gastrointestinal bleeding risk among the individual NOACs. This trend of reduced risk for upper gastrointestinal bleeding in NOACs compared to warfarin was consistent for both regular and reduced doses, throughout bleeding risk groups, and other subgroup analyses. NOACs were also associated with lower risk of death compared to warfarin. The risk for ischemic stroke was not significantly different among the oral anticoagulants in patients with atrial fibrillation. CONCLUSION: In patients on oral anticoagulant and PPI co-therapy, NOACs were associated with lower risk of upper gastrointestinal bleeding and mortality compared to warfarin, while there was no difference among the oral anticoagulants for stroke prevention. In patients on PPI therapy, NOACs may preferred over warfarin for decreasing risk of upper gastrointestinal bleeding and mortality.

γ-Oryzanol Improves Exercise Endurance and Muscle Strength by Upregulating PPARδ and ERRγ Activity in Aged Mice.

SCOPE: γ-Oryzanol, a well-known antioxidant, has been used by body builders and athletes to boost strength and increase muscle gain, without major side effects. However, the effect of γ-Oryzanol on sarcopenia and the underlying molecular mechanism is poorly understood. RESULTS: Aged mice fed with the γ-Oryzanol diet do not show significant changes in muscle weight, but show increased running endurance as well as improved grip strength. The expression and activity of PPARδ and ERRγ are increased in skeletal muscle of γ-Oryzanol supplemented mice. γ-Oryzanol upregulates oxidative muscle fibers by MEF2 transcription factor, and PGC-1α and ERRα expressions. Fatty acid oxidation related genes and mitochondria biogenesis are upregulated by γ-Oryzanol. In addition, γ-Oryzanol inhibits TGF-ß-Smad-NADPH oxidase 4 pathway and inflammatory cytokines such as TNF-α, IL-1ß, IL-6, and p65 NF-κB subunit, which cause skeletal muscle weakness. Collectively, γ-Oryzanol attenuates muscle weakness pathway and increases oxidative capacity by increasing PPARδ and ERRγ activity, which contributes to enhance strength and improve oxidative capacity in muscles, consequently enhancing exercise capacity in aged mice. Particularly, γ-Oryzanol directly binds to PPARδ. CONCLUSIONS: These are the first findings showing that γ-Oryzanol enhances skeletal muscle function in aged mice by regulating PPARδ and ERRγ activity without muscle gain.

Sex differences in the prognosis of patients with hypertrophic cardiomyopathy.

We investigated sex-related differences in the prognosis of patients with hypertrophic cardiomyopathy (HCM) using the Korea National Health Insurance Service database. From 2010 to 2016, 9524 patients diagnosed with HCM and had more than 1-year follow-up period were analyzed. The primary endpoint was the composite of cardiovascular death or new-onset heart failure (HF) admission. Propensity score-matching analysis was performed to adjust for different baseline characteristics. With a 4.4-years' median follow-up interval (range 2.0-6.6 years) and male predominance (77.6%), women with HCM were older (52.6 ± 9.7 vs. 51.4 ± 9.1, p < 0.001), had lower incomes, more comorbidities based on Charlson comorbidity index. Women with HCM had a higher incidence of the primary endpoint than men (incidence rate: 34.15 vs. 22.83 per 1000 person-years, log-rank p < 0.001). Multivariable Cox analysis showed that female sex was a poor prognostic factor for the primary endpoint (HR 1.43, 95% CI 1.24-1.64, p < 0.001). This was mainly driven by a higher incidence of new-onset HF admission (HR 1.55, 95% CI 1.34-1.80). However, there was no difference in the incidence of cardiovascular death between the sexes. This result was concordant in the propensity score-matched cohort. In conclusion, women with HCM have worse prognosis, which was mainly driven by a higher new-onset HF admission.

Chrysanthemum zawadskil Herbich attenuates dexamethasone-induced muscle atrophy through the regulation of proteostasis and mitochondrial function.

Chrysanthemum zawadskii Herbich (CZH) is used in traditional medicine to treat inflammatory diseases and diabetes. However, the effects of CZH on muscle wasting remains to be studied. Here, we investigated the effect of CZH on dexamethasone (DEX), a synthetic glucocorticoid, induced muscle atrophy. To examine the effect of CZH on muscle atrophy, C2C12 myotubes were co-treated with DEX and CZH for 24 h. The treatment with CZH prevented DEX-induced myotube atrophy in a dose-dependent manner. CZH inhibited the DEX-induced decrease of the MHC isoforms and the upregulation of atrogin-1 and MuRF1 in C2C12 differentiated cells. C57BL/6 mice were supplemented with 0.1 % CZH for 8 weeks, with DEX-induced muscle atrophy stimulated in the last 3 weeks. In the mice, CZH supplementation effectively reversed DEX-induced skeletal muscle atrophy and increased the exercise capacity of the mice through the inhibition of glucocorticoid receptor translocation. Additionally, we observed that DEX-evoked impaired proteostasis was ameliorated via the Akt/mTOR pathway. CZH also prevented the DEX-induced decrease in the mitochondrial respiration. HPLC analysis demonstrated the highest concentration of acacetin-7-O-ß-d-rutinoside (AR) among 4 compounds. Moreover, AR, a functional compound of CZH, prevented DEX-evoked muscle atrophy. Thus, we suggest that CZH could be a potential therapeutic candidate against muscle atrophy and AR is the main functional compound of CZH.

Determinants of rural-urban differences in health care provider visits among women of reproductive age in the United States.

BACKGROUND: Rural health disparities and access gaps may contribute to higher maternal and infant morbidity and mortality. Understanding and addressing access barriers for specialty women's health services is important in mitigating risks for adverse childbirth events. The objective of this study was to investigate rural-urban differences in health care access for women of reproductive age by examining differences in past-year provider visit rates by provider type, and quantifying the contributing factors to these findings. METHODS AND FINDINGS: Using a nationally-representative sample of reproductive age women (n = 37,026) from the Medical Expenditure Panel Survey (2010-2015) linked to the Area Health Resource File, rural-urban differences in past-year office visit rates with health care providers were examined. Blinder-Oaxaca decomposition analysis quantified the portion of disparities explained by individual- and county-level sociodemographic and provider supply characteristics. Overall, there were no rural-urban differences in past-year visits with women's health providers collectively (65.0% vs 62.4%), however differences were observed by provider type. Rural women had lower past-year obstetrician-gynecologist (OB-GYN) visit rates than urban women (23.3% vs. 26.6%), and higher visit rates with family medicine physicians (24.3% vs. 20.9%) and nurse practitioners/physician assistants (NPs/PAs) (24.6% vs. 16.1%). Lower OB-GYN availability in rural versus urban counties (6.1 vs. 13.7 providers/100,000 population) explained most of the rural disadvantage in OB-GYN visit rates (83.8%), and much of the higher family physician (80.9%) and NP/PA (50.1%) visit rates. Other individual- and county-level characteristics had smaller effects on rural-urban differences. CONCLUSION: Although there were no overall rural-urban differences in past-year visit rates, the lower OB-GYN availability in rural areas appears to affect the types of health care providers seen by women. Whether rural women are receiving adequate specialized women's health care services, while seeing a different cadre of providers, warrants further investigation and has particular relevance for women experiencing high-risk pregnancies and deliveries.

Green Tomato Extract Prevents Bone Loss in Ovariectomized Rats, a Model of Osteoporosis.

Although drug therapies are available for postmenopausal osteoporosis, these drugs are not free of side effects and long-term adherence to them are low. A safe and effective nutritional approach to counter postmenopausal osteoporosis is an important research goal. We fed ovariectomized (OVX) Sprague-Dawley rats a diet supplemented with 1% or 2% green tomato extract (GTE). After 12 weeks, micro-computed tomography scans revealed that GTE supplementation effectively prevented distal femur bone loss. This prevention was due to improved bone formation and suppressed bone resorption as observed by the regulation of osteoblast and osteoclast activities. GTE supplementation also improved bone formation through Bmp2-Smad 1/5/8-Runx2 signaling, while bone resorption was regulated by the receptor activator of nuclear factor kappa-B (RANKL)/osteoprogeterin (OPG) pathway. These results suggest that GTE supplementation prevents severe postmenopausal bone loss by maintaining the regulation of bone homeostasis in OVX rats. GTE as a diet supplement might be a potential novel alternative for the prevention of postmenopausal osteoporosis.

Dry-Fermented Soybean Food (Cheonggukjang) Ameliorates Senile Osteoporosis in the Senescence-Accelerated Mouse Prone 6 Model.

Senile osteoporosis increases the risk of skeletal fractures with age. Cheonggukjang (CGJ), a traditional Korean dry fermented soybean product, has numerous therapeutic effects; however, its effects on bone mineral density (BMD) and bone metabolism in senile osteoporosis are unclear. In this study, we treated the senescence-accelerated mouse prone 6 (SAMP6) model of senile osteoporosis with CGJ to determine its potential for ameliorating and preventing osteoporosis progression. High-performance liquid chromatography analysis for isoflavone profiles revealed that short-term fermentation significantly increased the isoflavone aglycone content in soybeans. Thereafter, we fed 6-week-old SAMP6 mice with experimental diets containing 5% or 10% CGJ for 15 weeks. Microcomputed tomography revealed that CGJ supplementation effectively increased the BMD and relative bone length. In vitro, CGJ increased the osteopontin reactivity and upregulated the expression of Alp, Col1a1, Fak, Bmp2/4, Smad1/5/8, and Runx2 in osteoblasts, and decreased Cathepsin K reactivity and downregulated Rankl and Nfatc1 expression in osteoclasts. In addition, CGJ increased the osteoprotegerin/Rankl ratio. Collectively, these results demonstrate that CGJ can ameliorate the detrimental effects of senile osteoporosis by improving osteogenesis and decreasing osteoclast activity.

Fermentation Improves the Preventive Effect of Soybean Against Bone Loss in Senescence-Accelerated Mouse Prone 6.

Osteopenia is a preclinical phase of osteoporosis, it occurs naturally with aging and increases the risk of bone fractures in elderly males. Previous studies have revealed the beneficial effects of soybean on preventing bone loss due to its isoflavone contents. Fermentation alters the soybean isoflavone contents, that is, isoflavone glucosides is hydrolyzed into aglycones. However, it is not clear how these alterations influences the preventive effect of soybean on bone loss. In this study, we fed senescence-accelerated mouse prone 6 (SAMP6), a model of senile osteopenia, with an equal dosage of nonfermented soybean (NS) or fermented soybean, Doenjang (DJ) for 18 weeks. Mice supplemented with DJ showed 1.13-fold higher bone densities and 1.06-fold longer relative bone lengths than those of osteopenic SAMP6 mice old control (OC), while NS-supplemented mice showed no significant improvement. Supplementation with DJ effectively prevented bone loss in the osteopenia model by the improvement of bone formation and reduction of osteoclastogenesis. In addition, we discovered that DJ increased osteogenesis in SAMP6 mice via BMP2-Smad-Runx2 signaling. These results suggest that the fermentation process could enhance bone loss prevention by soybean and dietary supplementation with fermented soybeans may be beneficial for bone health. PRACTICAL APPLICATION: Soybean fermentation improved the preventive effects of soybean on bone loss. Therefore, the consumption of fermented soybean, Doenjang, is a potential alternative for aging-related bone loss therapy.

Dihydrodaidzein and 6-hydroxydaidzein mediate the fermentation-induced increase of antiosteoporotic effect of soybeans in ovariectomized mice.

The consumption of soybeans is known to have beneficial effects on osteoporosis in postmenopausal women. However, the effects of soybean fermentation on the bioavailability and the antiosteoporotic effect have not yet been elucidated. To address this question, we fed ovariectomized C57BL/6J mice with a 5% nonfermented raw soybean (RS)- or fermented soybean (FS)-supplemented diet. After 18 wk of treatment, microcomputed tomography showed that FSs significantly increased bone mineral density compared with RSs. This was because of the up-regulation of bone morphogenic protein 2 (Bmp2) and its downstream target osteopontin in bone tissues. We analyzed isoflavone metabolite profiles in the sera of RS- or FS-fed mice and observed that the levels of 19 isoflavone metabolites were significantly increased in the sera of FS-fed mice. Among these metabolites, we observed that both dihydrodaidzein (DHD) and 6-hydroxydaidzein (6-HD) increased osteogenesis via Bmp2 signaling pathway in MC3T3-E1 cells and reduced receptor activator of nuclear factor κ-B ligand-induced osteoclastogenesis in RAW264.7 cells through the inhibition of NF-κB activation and MAPK phosphorylation. These data suggest that improved bioavailability of FSs resulted from the production of active metabolites such as DHD and 6-HD after consumption. DHD and 6-HD can be used as potential therapeutics for the amelioration of osteoporotic bone loss.-Kim, J.-S., Lee, H., Nirmala, F. S., Jung, C. H., Kim, M. J., Jang, Y.-J., Ha, T. Y., Ahn, J. Dihydrodaidzein and 6-hydroxydaidzein mediate the fermentation-induced increase of anti-osteoporotic effect of soybeans in ovariectomized mice.

Proteinuria Detected by Urine Dipstick Test as a Risk Factor for Atrial Fibrillation: A Nationwide Population-Based Study.

Proteinuria is one of the well-known risk factors for cardiovascular disease. However the impact of proteinuria on the incidence of atrial fibrillation (AF) is unclear. In this study, we investigated the association between proteinuria detected using urine dipstick test and the risk of AF. A total of 18,201,275 individuals were analyzed, who had no prior AF and had received biennial health checkups provided by the National Health Insurance Service between 2005 and 2008 in Korea. Incidences of AF were ascertained through the end of 2015. During a mean follow-up of 9.6 years, a total of 324,764 (1.8%) developed AF (1.86 per 1,000 person-years). In Cox regression models, proteinuria was associated with an increased risk of AF: adjusted HR and 95% CI of AF occurrence were 1.13 (1.10-1.16), 1.34 (1.31-1.38), 1.53 (1.48-1.58), 1.82 (1.71-1.94), and 1.86 (1.61-2.16) in individuals with trace, 1+, 2+, 3+, and 4+ proteinuria, respectively, compared with those without proteinuria. The result was consistent even after additional adjustment for estimated glomerular filtration rate. In addition, the risk of AF further increased or decreased according to the follow-up dipstick test results. Thus, proteinuria measured with a dipstick test might be considered a potent risk factor for AF development.

Tyrosol, an olive oil polyphenol, inhibits ER stress-induced apoptosis in pancreatic ß-cell through JNK signaling.

Dysfunction of pancreatic ß-cell is a major determinant for the development of type 2 diabetes. Because of the stimulated insulin secretion in metabolic syndrome, endoplasmic reticulum (ER) stress plays a central mediator for ß-cell failure. In this study, we investigated whether an antioxidant phenolic compound, tyrosol protects against ß-cell dysfunction associated with ER stress. To address this issue, we exposed pancreatic ß cells, NIT-1 to tunicamycin with tyrosol. We found tyrosol diminished tunicamycin-induced cell death in a dose-dependent manner. We also detected tyrosol decreased the expressions of apoptosis-related markers. Exposure to tunicamycin evoked UPR response and co-treatment of tyrosol led to reduction of ER stress. These effects of tyrosol were mediated by the phosphorylation of JNK. Moreover, we confirmed supplement of tyrosol ameliorated ß-cell loss induced by high fat feeding. Taken together, our study provides a molecular basis for signaling transduction of protective effect of tyrosol against ER stress-induced ß-cell death. Therefore, we suggest tyrosol could be a potential therapeutic candidate for amelioration of type 2 diabetes.

The stability of perceptual compensation for coarticulation within and across individuals: a cross-validation study.

Perceptual compensation for coarticulation (PCCA) refers to listener responses consistent with perceptual reduction of the acoustic effects of the coarticulatory context on a target sound. The robustness of PCCA across individuals and across tasks have not been studied together previously. This study reports the results of two experiments designed to determine the robustness of perceptual compensation for vocalic influence on sibilant perception across tasks and the stability of such compensatory response within an individual. Identification and discrimination data, collected in the laboratory and on Amazon's Mechanical Turk, showed that individuals are moderately stable in their PCCA responses across tasks and the level of stability is consistent across both the lab-based and the internet-based cohorts, although some differences are observed.

Eleutheroside E, An Active Component of Eleutherococcus senticosus, Ameliorates Insulin Resistance in Type 2 Diabetic db/db Mice.

Eleutheroside E (EE), a principal component of Eleutherococcus senticosus (ES), has anti-inflammatory and protective effects in ischemia heart. However, it is unknown whether it ameliorates insulin resistance and reduces hyperglycemia in diabetes. This study investigated the effect of EE-containing ES extracts, as well as EE, on hyperglycemia and insulin resistance in db/db mice. EE increased the insulin-provoked glucose uptake in C2C12 myotubes. Moreover, EE improved TNF- α -induced suppression of glucose uptake in 3T3-L1 adipocytes. Five-week-old db/db mice were fed a diet consisting of ES extract or EE for 5 weeks. Both were effective in improving serum lipid profiles and significantly decreased blood glucose and serum insulin levels. ES and EE supplementation effectively attenuated HOMA-IR. Glucose tolerance and insulin tolerance tests showed that EE increased insulin sensitivity. Immunohistochemical staining indicated that ES and EE protected pancreatic alpha and beta cells from diabetic damage. In addition, ES and EE improved hepatic glucose metabolism by upregulating glycolysis and downregulating gluconeogenesis in obese type 2 diabetic mice. These data suggest that EE mediates the hyperglycemic effects of ES by regulating insulin signaling and glucose utilization. The beneficial effects of EE may provide an effective and powerful strategy to alleviate diabetes.