A novel HDAC6 inhibitor interferes microtubule dynamics and spindle assembly checkpoint and sensitizes cisplatin-induced apoptosis in castration-resistant prostate cancer.

BACKGROUND: Metastatic castration-resistant prostate cancer (CRPC), the most refractory prostate cancer, inevitably progresses and becomes unresponsive to hormone therapy, revealing a pressing unmet need for this disease. Novel agents targeting HDAC6 and microtubule dynamics can be a potential anti-CRPC strategy. METHODS: Cell proliferation was examined in CRPC PC-3 and DU-145 cells using sulforhodamine B assay and anchorage-dependent colony formation assay. Flow cytometric analysis of propidium iodide staining was used to determine cell-cycle progression. Cell-based tubulin polymerization assay and confocal immunofluorescence microscopic examination determine microtubule assembly/disassembly status. Protein expressions were determined using Western blot analysis. RESULTS: A total of 82 novel derivatives targeting HDAC6 were designed and synthesized, and Compound 25202 stood out, showing the highest efficacy in blocking HDAC6 (IC50, 3.5 nM in enzyme assay; IC50, 1.0 µM in antiproliferative assay in CRPC cells), superior to tubastatin A (IC50, 5.4 µM in antiproliferative assay). The selectivity and superiority of 25202 were validated by examining the acetylation of both α-tubulin and histone H3, detecting cell apoptosis and HDACs enzyme activity assessment. Notably, 25202 but not tubastatin A significantly decreased HDAC6 protein expression. 25202 prolonged mitotic arrest through the detection of cyclin B1 upregulation, Cdk1 activation, mitotic phosphoprotein levels, and Bcl-2 phosphorylation. Compound 25202 did not mimic docetaxel in inducing tubulin polymerization but disrupted microtubule organization. Compound 25202 also increased the phosphorylation of CDC20, BUB1, and BUBR1, indicating the activation of the spindle assembly checkpoint (SAC). Moreover, 25202 profoundly sensitized cisplatin-induced cell death through impairment of cisplatin-evoked DNA damage response and DNA repair in both ATR-Chk1 and ATM-Chk2 pathways. CONCLUSION: The data suggest that 25202 is a novel selective and potent HDAC6 inhibitor. Compound 25202 blocks HDAC6 activity and interferes microtubule dynamics, leading to SAC activation and mitotic arrest prolongation that eventually cause apoptosis of CRPC cells. Furthermore, 25202 sensitizes cisplatin-induced cell apoptosis through impeding DNA damage repair pathways.

Unveiling the multifaceted nexus of subjective aging, biological aging, and chronological age: Findings from a nationally representative cohort study.

OBJECTIVES: This study aims to investigate how subjective aging influences the psychological and behavioral responses of older individuals, specifically focusing on the associations between subjective aging and longitudinal changes in biological age. METHODS: This is a retrospective cohort study retrieving data from the Taiwan Longitudinal Study on Aging (TLSA), over a 4-year follow-up period. Subjective aging is assessed by asking participants if they perceive themselves as old, while frailty is measured using a frailty index comprising 34 deficits from various domains. Participants are categorized into three groups based on their chronological age. The association between subjective aging and transition of biological age (as indicated by an increased frailty index) from 2011 to 2015 is examined using logistic regression models. RESULTS: The study consisted of 2412 participants, who were categorized into middle-age (n = 1,082), young-old (n = 779), and old-old (n = 551) groups. Among them, individuals exhibiting subjective aging at baseline were more likely to be older in chronological age, female, illiterate, and unemployed, compared to those without subjective aging. The adjusted odds ratios (aORs) for the association between subjective aging and an increased biological age were 1.72 [95% CI: 0.88-3.34], 1.61 [0.77-3.37], and 1.08 [0.65-1.80], in the middle-age, young-old, and old-old groups, respectively. DISCUSSIONS: No significant associations were found between changes in biological age and subjective aging across various chronological age groups. Notably, within the younger age group, a discernible trend towards an association was observed, indicating the potential age-related nuances in the complex interrelation between subjective age, biological aging, and chronological aging.

Effects of declines in personal mastery on self-perceived mobility, physical function, cognitive function, and depressive symptoms: a 6-year follow-up study from the Social Environment and Biomarkers of Aging Study.

OBJECTIVES: As the psychosocial competence, personal mastery helps individuals to cope with stressful life events, and this study aims to examine impacts of declines in personal mastery on healthy aging among community-dwelling middle-aged and older adults using a nationally representative cohort. METHODS: Data from 648 study participants in the Social Environment and Biomarkers of Aging Study (SEBAS) were retrieved for analysis. All participants were divided into four groups based on their baseline and changes of personal mastery (measured by the Pearlin mastery score) during the 6-year follow-up. Multivariate logistic regression models were adopted to examine associations between declines in personal mastery and indicators for healthy aging (declines in self-perceived mobility, physical function (activities of daily living (ADLs) and instrumental activities of daily living (IADLs)), cognitive function and depressive symptoms). RESULTS: After adjustments for demographics and comorbidities, those with declines in personal mastery were associated with greater risks of declines in self-perceived mobility (adjusted odds ratio (aOR) 1.50 [95% confidence interval 1.01-2.22], p < 0.05). Although the point estimate in the unadjusted models indicated similar associations between declines in personal mastery and declines in ADLs, IADLs, cognitive function or depressive symptoms, these outcomes did not reach statistical significance in the adjusted model. CONCLUSIONS: Declines in personal mastery were negatively associated with indicators related to healthy aging (particularly locomotion) in a 6-year follow-up. Further investigations are needed to explore the effects of preventing declines in personal mastery in promoting healthy aging over time.

Double-layered PLGA/HA microneedle systems as a long-acting formulation of polyphenols for effective and long-term management of atopic dermatitis.

Atopic dermatitis (AD) is a chronic, relapsing inflammatory disorder that requires long-term treatment to achieve optimal control. Topical corticosteroids or calcineurin inhibitors are the mainstay of treatment, but the safety and efficacy of their daily use remain a concern. Here, we report a double-layered poly(lactic-co-glycolic acid) (PLGA)/sodium hyaluronate (HA) microneedle (MN) patch as a long-acting formulation for sustained delivery of natural polyphenols, curcumin (CUR) and gallic acid (GA), into the inflamed skin. Upon insertion into the skin, the HA layer is rapidly dissolved within 5 min for triggering GA release; the PLGA tip is embedded into the dermis for sustained release of CUR for 2 months. Initially, CUR and GA are simultaneously released from the MNs to exert synergistic antioxidant and anti-inflammatory effects, thus promptly relieving AD symptoms. After the complete release of GA, the extended CUR release can maintain the improvement obtained for at least 56 days. Our results revealed that compared with the CUR-only MN and untreated AD groups, the administration of CUR/GA-loaded MNs not only rapidly reduced the dermatitis score from Day 2 but also significantly inhibited epidermal hyperplasia and mast cell accumulation, reduced serum IgE and histamine levels, and downregulated reactive oxygen species production in the skin lesions of Nc/Nga mice on Day 56. These findings demonstrated that the double-layered PLGA/HA MN patch can serve as an effective dual-polyphenol delivery system for rapid and long-term management of AD.

Association between maternal benzodiazepine or Z-hypnotic use in early pregnancy and the risk of stillbirth, preterm birth, and small for gestational age: a nationwide, population-based cohort study in Taiwan.

BACKGROUND: Benzodiazepines and Z-hypnotics are commonly prescribed for anxiety and insomnia during pregnancy, but the evidence regarding potential adverse neonatal outcomes is insufficient because of poor control for confounding factors in previous studies. We therefore aimed to evaluate the association between the use of benzodiazepines or Z-hypnotics during early pregnancy and adverse neonatal outcomes (stillbirth, preterm birth, and small for gestational age). METHODS: We did a nationwide, population-based cohort study in Taiwan using three data sources: Taiwan's National Birth Certificate Application database, the National Health Insurance database, and the Maternal and Child Health Database. The study cohort included all singleton pregnancies of females aged 15-50 years who gave birth between Jan 1, 2004, and Dec 31, 2018. Pregnancies without valid information were excluded. Benzodiazepine and Z-hypnotic use was defined as at least one benzodiazepine or Z-hypnotic prescription during early pregnancy (the first 20 weeks of pregnancy). The primary outcomes were stillbirth (fetal death at or after 20 weeks' gestation), preterm birth (<37 weeks' gestation), and small for gestational age (birthweight below the 10th percentile for gestational age by sex). Logistic regression models with propensity score fine stratification weighting were used to control for potential confounders and examine the association between benzodiazepines or Z-hypnotics use during early pregnancy and the risk of adverse neonatal outcomes. Odds ratios (ORs) and 95% CIs were reported. We used confounding by indication control analyses, a sibling control study, and a paternal negative control design to account for unmeasured confounders. The risk associated with exposure during late pregnancy was also assessed. FINDINGS: Between Oct 7, 2021, and June 10, 2022, we analysed the study data. The cohort included 2 882 292 singleton pregnancies; of which, 75 655 (2·6%) of the mothers were dispensed one or more benzodiazepines or Z-hypnotics during early pregnancy. Women exposed during pregnancy were older (mean age at delivery was 31·0 years [SD 5·3] for exposed women vs 30·6 years [4·9] for unexposed women), had a higher prevalence of psychiatric disorders, and were more likely to have unhealthy lifestyle behaviours than unexposed women. Information about ethnicity was not available. Early pregnancy exposure was associated with adverse neonatal outcomes compared with non-exposure. The propensity score-weighted OR was 1·19 (95% CI 1·10-1·28) for stillbirth, 1·19 (1·16-1·23) for preterm birth, and 1·16 (1·13-1·19) for small for gestational age. After controlling for confounding by indication, there was no significant association between drug exposure and stillbirth risk; however, this attenuation was not observed for preterm birth and small for gestational age. In models with sibling controls that accounted for familial confounding and genetic factors, early exposure to benzodiazepines or Z-hypnotics was not associated with an increased risk of stillbirth and preterm birth, but it remained significantly associated with small for gestational age. The paternal negative control analyses with point estimates close to the null indicated no strong evidence of unmeasured confounding shared by the mother and the father. Substantially increased risks of stillbirth and preterm birth were observed for late pregnancy exposure. INTERPRETATION: Benzodiazepine or Z-hypnotic use in early pregnancy is not associated with a substantial increase in the risk of stillbirth and preterm birth after accounting for unmeasured confounding factors. Clinicians should be aware of the increased risk of small for gestational age and caution should be taken when prescribing these medications during late pregnancy. FUNDING: National Science and Technology Council, Taiwan. TRANSLATION: For the Taiwanese translation of the abstract see Supplementary Materials section.

Quercetin supplementation attenuates cisplatin induced myelosuppression in mice through regulation of hematopoietic growth factors and hematopoietic inhibitory factors.

The present study investigated the effects of quercetin on cisplatin (CDDP)-induced common side effect, myelosuppression, and the possible mechanisms in Balb/c mice. The mice were randomly treated with CDDP alone or in combination with quercetin for 14 days. Quercetin was given by intraperitoneal injection (10 mg/kg, 3 times a week; IQ) or by a diet containing 0.1% or 1% quercetin (LQ and HQ, respectively). We found that quercetin supplementation especially HQ and IQ, significantly restored the decrease in number of bone marrow cells, total white blood cells, red blood cells and platelets, and the body weight in mice exposed to CDDP (P≤.05). Similar trends were observed in the number of neutrophils, lymphocytes and monocytes in the plasma. HQ and IQ also increased the levels of hematopoietic growth factors (HGFs), especially in granulocyte-macrophage-colony stimulating factor and IL-9 (P<.05), but decreased the levels of hematopoietic inhibitory factors (HIFs) and oxidative stress in the plasma and the bone marrow in CDDP-exposed mice. Furthermore, both quercetin and quercetin-3-O-glucuronide (Q3G) significantly increase cell viability and inhibited apoptosis at 48 or 72 h (P≤.05), accompanied by increasing HGF levels and decreasing HIF levels in the cultured medium in 32D cells exposed to CDDP. IL-9 siRNA transfection suppressed the effects of quercetin and Q3G on cell viability (P≤.05) in32D cells. In conclusion, our results indicate that quercetin attenuates CDDP-induced myelosuppression through the mechanisms associated with regulation of HGFs and HIFs.

Matriptase-2/NR4A3 axis switches TGF-ß action toward suppression of prostate cancer cell invasion, tumor growth, and metastasis.

Dysregulation of pericellular proteolysis is strongly implicated in cancer metastasis through alteration of cell invasion and the microenvironment. Matriptase-2 (MT-2) is a membrane-anchored serine protease which can suppress prostate cancer (PCa) cell invasion. In this study, we showed that MT-2 was down-regulated in PCa and could suppress PCa cell motility, tumor growth, and metastasis. Using microarray and biochemical analysis, we found that MT-2 shifted TGF-ß action towards its tumor suppressor function by repressing epithelial-to-mesenchymal transition (EMT) and promoting Smad2 phosphorylation and nuclear accumulation to upregulate two TGF-ß1 downstream effectors (p21 and PAI-1), culminating in hindrance of PCa cell motility and malignant growth. Mechanistically, MT-2 could dramatically up-regulate the expression of nuclear receptor NR4A3 via iron metabolism in PCa cells. MT-2-induced NR4A3 further coactivated Smad2 to activate p21 and PAI-1 expression. In addition, NR4A3 functioned as a suppressor of PCa and mediated MT-2 signaling to inhibit PCa tumorigenesis and metastasis. These results together indicate that NR4A3 sustains MT-2 signaling to suppress PCa cell invasion, tumor growth, and metastasis, and serves as a contextual factor for the TGF-ß/Smad2 signaling pathway in favor of tumor suppression via promoting p21 and PAI-1 expression.

Privacy Concerns and Continued Use Intention of Telemedicine During COVID-19.

Introduction: Privacy concerns are a major barrier to online technology adoption. However, when consumers are facing personal risks (being ill) and environmental risks (pandemic), the effect of privacy concerns on continued use intention of telemedicine is unknown. The large user pool of virtual visits during COVID-19 provides a great opportunity to understand consumers' privacy concerns when facing personal and environmental risks. Objective: This research investigates how patients weigh personal risks (e.g., illness) and environmental risks (e.g., pandemic) against privacy concerns when deciding whether to utilize telemedicine as an option for being treated for an acute illness. Methods: Respondents (1,059 qualified) meeting the following criteria: ≥18 years old, U.S. residents, virtual patient for acute conditions during COVID-19, and a Human Intelligence Task approval rate of >95%, were recruited utilizing Amazon Mechanical Turk during the middle of the pandemic. An online survey was conducted to collect data. Results: Analysis indicates that first-time telepatients (82% of respondents) have greater privacy concerns than repeat users. Findings also indicate that patients who are female and have some college education or less reported greater privacy concerns. Interestingly, privacy concerns are positively related to continued use intention. This result holds when satisfaction and user characteristics are controlled. Conclusions: When consumers are ill, privacy concerns still play an important role in telemedicine adoption. However, under environmental risks such as the COVID-19 pandemic, privacy concerns do not negatively impact their continued use intention, and satisfaction is positively associated with continued use intention.

Impact of coinfection status and comorbidity on disease severity in adult emergency department patients with influenza B.

BACKGROUND: Influenza B accounts for approximately one fourth of the seasonal influenza burden. However, research on the importance of influenza B has received less attention compared to influenza A. We sought to describe the association of both coinfections and comorbidities with disease severity among adults presenting to emergency departments (ED) with influenza B. METHODS: Nasopharyngeal samples from patients found to be influenza B positive in four US and three Taiwanese ED over four consecutive influenza seasons (2014-2018) were tested for coinfections with the ePlex RP RUO panel. Multivariable logistic regressions were fitted to model adjusted odds ratios (aOR) for two severity outcomes separately: hospitalization and pneumonia diagnosis. Adjusting for demographic factors, underlying health conditions, and the National Early Warning Score (NEWS), we estimated the association of upper respiratory coinfections and comorbidity with disease severity (including hospitalization or pneumonia). RESULTS: Amongst all influenza B positive individuals (n = 446), presence of another upper respiratory pathogen was associated with an increased likelihood of hospitalization (aOR = 2.99 [95% confidence interval (95% CI): 1.14-7.85, p = 0.026]) and pneumonia (aOR = 2.27 [95% CI: 1.25-4.09, p = 0.007]). Chronic lung diseases (CLD) were the strongest predictor for hospitalization (aOR = 3.43 [95% CI: 2.98-3.95, p < 0.001]), but not for pneumonia (aOR = 1.73 [95% CI: 0.80-3.78, p = 0.166]). CONCLUSION: Amongst ED patients infected with influenza B, the presence of other upper respiratory pathogens was independently associated with both hospitalization and pneumonia; presence of CLD was also associated with hospitalization. These findings may be informative for ED clinician's in managing patients infected with influenza B.

Quercetin attenuates cisplatin-induced fat loss.

PURPOSE: The major aim of the present study was to determine the effects of quercetin, a well-known flavonoid, on attenuating cisplatin (CDDP)-induced fat loss and the possible mechanisms. METHODS: Tumor-bearing nude mice and tumor-free BALB/c mice were administrated with CDDP alone or in combination with quercetin by a diet containing 0.1% or 1% quercetin (LQ or HQ) or by intraperitoneal injection (IQ) to determine the effects of quercetin on the anticancer effect of CDDP or CDDP-induced fat loss. The effects of quercetin on fat accumulation in CDDP-exposed 3T3-L1 cells were also determined. RESULTS: We first showed that HQ and IQ significantly enhanced the anticancer effect of CDDP by upregulating p53- and p21-associated pathways, while tended to attenuate CDDP-induced fat loss in tumor-bearing nude mice. The study in 3T3-L1 cells showed that CDDP decreased the fat accumulation accompanied by strong upregulation of the expression of six genes which are associated with fat metabolism, while quercetin completely suppressed such an effect. The tumor-free BALB/c mice study consistently showed a protective effect of HQ on CDDP-induced body weight and epididymal fat loss. HQ also increased the fat levels in liver and muscle tissues. In epididymal fat tissues, HQ consistently attenuated CDDP-induced changes in fat metabolism-associated gene expression. However, CDDP alone or in combination with HQ did not affect the food intake. CONCLUSIONS: This study demonstrates that quercetin possesses the potential to suppress CDDP-induced fat loss may partly through the regulation of the fat metabolism-associated gene expression.

Telemedicine for Acute Conditions During COVID-19: A Nationwide Survey Using Crowdsourcing.

Background: COVID-19 has resulted in a rapid and significant adoption of telemedicine for acute conditions. Understanding whether patient demand will last after the pandemic helps providers and payers make informed decisions about whether to continue adopting telemedicine. Objective: We examine user experience as well as process and patient outcomes of using telemedicine for acute conditions during COVID-19 and assess how patient outcomes are affected by waiting times and demographics. Materials and Methods: A survey was conducted via Amazon Mechanical Turk during June 17-29, 2020. Inclusion criteria were: (1) ≥18 years old, (2) residing in the United States, (3) used telemedicine for acute conditions after January, and 4) a human intelligence task approval rate of >95%. Process outcomes included patient waiting time with patient outcomes being satisfaction and future use intention. Bivariate analysis and regressions of the data were performed. Results: On average, respondents reported appointment wait time of 2.76 days and virtual office wait time of 19.44 min. Overall, respondents reported moderate satisfaction (mean 5.08-5.35 of 7) and future use intention (mean 5.10-5.32 of 7). Over 72% of the respondents were satisfied and had future use intention. Females, heavier internet users, and those on the higher/lower ends of the education spectrum reported better patient outcomes. Patients "visiting" a doctor experiencing eye problems, vis-à-vis other ailments, reported lower satisfaction and intention. Waiting time negatively associates with satisfaction. Conclusions: Given the satisfactory outcomes, the high demand for telemedicine may continue after the COVID-19 pandemic. However, whether providers will continue to offer telemedicine visits may require more evidence.

Impact of Pediatric Mobile Game Play on Healthy Eating Behavior: Randomized Controlled Trial.

BACKGROUND: Video and mobile games have been shown to have a positive impact on behavior change in children. However, the potential impact of game play patterns on outcomes of interest are yet to be understood, especially for games with implicit learning components. OBJECTIVE: This study investigates the immediate impact of fooya!, a pediatric dietary mobile game with implicit learning components, on food choices. It also quantifies children's heterogeneous game play patterns using game telemetry and determines the effects of these patterns on players' food choices. METHODS: We analyzed data from a randomized controlled trial (RCT) involving 104 children, aged 10 to 11 years, randomly assigned to the treatment group (played fooya!, a dietary mobile game developed by one of the authors) or the control group (played Uno, a board game without dietary education). Children played the game for 20 minutes each in two sessions. After playing the game in each session, the children were asked to choose 2 out of 6 food items (3 healthy and 3 unhealthy choices). The number of healthy choices in both sessions was used as the major outcome. We first compared the choice and identification of healthy foods between treatment and control groups using statistical tests. Next, using game telemetry, we determined the variability in game play patterns by quantifying game play measures and modeled the process of game playing at any level across all students as a Markov chain. Finally, correlation tests and regression models were used to establish the relationship between game play measures and actual food choices. RESULTS: We saw a significant main effect of the mobile game on number of healthy foods actually chosen (treatment 2.48, control 1.10; P<.001; Cohen d=1.25) and identified (treatment 7.3, control 6.94; P=.048; Cohen d=.25). A large variation was observed in children's game play patterns. Children played an average of 15 game levels in 2 sessions, with a range of 2 to 23 levels. The greatest variation was noted in the proportion of scoring activities that were highly rewarded, with an average of 0.17, ranging from 0.003 to 0.98. Healthy food choice was negatively associated with the number of unhealthy food facts that children read in the game (Kendall τ=-.32, P=.04), even after controlling for baseline food preference. CONCLUSIONS: A mobile video game embedded with implicit learning components showed a strong positive impact on children's food choices immediately following the game. Game telemetry captured children's different play patterns and was associated with behavioral outcomes. These results have implications for the design and use of mobile games as an intervention to improve health behaviors, such as the display of unhealthy food facts during game play. Longitudinal RCTs are needed to assess long-term impact. TRIAL REGISTRATION: ClinicalTrials.gov NCT04082195; https://clinicaltrials.gov/ct2/show/NCT04082195, registered retrospectively.

A Pilot Clinical Study of Liquid Ubiquinol Supplementation on Cardiac Function in Pediatric Dilated Cardiomyopathy.

BACKGROUND: Pediatric dilated cardiomyopathy (PDCM) is a life-threatening type of cardiac muscle dysfunction in children. Ubiquinone is a lipid-soluble nutrient that participates in energy synthesis. Recently, a novel hydrophilic ubiquinol supplement was developed. The purpose of this study was to assess the effect of liquid ubiquinol supplementation (10 mg/kg body weight/day) on cardiac function in children with PDCM. METHODS: Ten children diagnosed with PDCM were recruited to this study and administered with liquid ubiquinol for 24 weeks. The cardiac function was measured by echocardiography. The New York Heart Association (NYHA) functional classification was used to assess symptoms of heart failure. Plasma coenzyme Q10 levels were measured during the study. RESULTS: Ejection fraction (EF) and fractional shortening (FS) were significantly higher than the baseline values until week 16 of supplementation. Subjects who had higher plasma coenzyme Q10 concentration had significantly better EF and FS values. In addition, 30% of the subjects showed improvement in the NYHA classification after 24 weeks of supplementation. CONCLUSION: Liquid ubiquinol supplementation is associated with an increase the level of coenzyme Q10 to complementary improve cardiac function (particularly EF and FS) and ameliorate the symptoms of heart failure in children with PDCM.

Does coffee drinking have beneficial effects on bone health of Taiwanese adults? A longitudinal study.

BACKGROUND: Results from studies investigating the association between coffee consumption and osteoporosis or bone mineral density (BMD) have been inconsistent. This longitudinal study was performed to assess the effect of coffee drinking on bone health of Taiwanese adults. METHODS: Data were retrieved from the Li-Shin (Landseed) Hospital in Taoyuan City. In 2006, 6152 participants completed a questionnaire on coffee drinking and other lifestyle factors. In 2014, 5077 of them were followed up. Nonetheless, a total of 2395 participants with incomplete data were excluded. The final analyses included 2682 participants comprising 1195 men and 1487 women (706 premenopausal and 781 postmenopausal). T-scores were derived from the osteo-sono assessment index (OSI) which is a surrogate of BMD. Coffee drinking was categorized as "no, medium, and high" based on the number of cups that were consumed per week in both 2006 and 2014. RESULTS: In general, medium and high coffee drinking were associated with higher T-scores. However, significant results were observed only among high drinkers (ß = 0.158; P = 0.0038). Nonetheless, the test for linear trend was significant (P = 0.0046). After stratification by sex, medium and high coffee drinking were associated with higher T-scores. However, significant results were prominent only among high male drinkers (ß = 0.237; P = 0.0067) and the test for trend was significant (P = 0.0161). Based on menopausal status, coffee drinking was associated with higher T-scores. Nevertheless, significant results were found only among premenopausal women (ß = 0.233; P = 0.0355 and ß = 0.234; P = 0.0152 for medium and high coffee drinking, respectively. The test for linear trend was significant (P = 0.0108). CONCLUSION: Coffee drinking was significantly associated with higher T-scores hence, a lower risk of osteoporosis in men and premenopausal women.

Effect of liquid ubiquinol supplementation on glucose, lipids and antioxidant capacity in type 2 diabetes patients: a double-blind, randomised, placebo-controlled trial.

Ubiquinone is a lipid antioxidant, and a novel liquid ubiquinol (a hydro-soluble, reduced form of coenzyme Q10) supplement was recently developed. The purpose of this study was to examine the levels of glucose, lipids and antioxidant capacity of type 2 diabetes patients after liquid ubiquinol supplementation. This study was designed as a randomised, double-blind, placebo-controlled trial. In all, fifty participants were randomly assigned to a placebo (n 25) or liquid ubiquinol (100 mg/d, n 25) group, and the intervention lasted for 12 weeks. Plasma coenzyme Q10, glucose homoeostasis parameters, lipid profiles, oxidative stress and antioxidative enzyme activities were measured during the study. After 12 weeks of supplementation, glyco Hb (HbA1c) value was significantly decreased in the liquid ubiquinol group (P=0·03), and subjects in the liquid ubiquinol group had significantly lower anti-glycaemic medication effect scores (MES) compared with those in the placebo group (P=0·03). The catalase (P<0·01) and glutathione peroxidase (P=0·03) activities were increased significantly after supplementation. Plasma coenzyme Q10 was correlated with the insulin level (P=0·05), homoeostatic model assessment-insulin resistance (P=0·07), quantitative insulin sensitivity check index (P=0·03) and the anti-hyperglycaemic agents' MES (P=0·03) after supplementation. Lipid profiles did not change after supplementation; however, the subjects in the placebo group had a significantly lower level of HDL-cholesterol after 12 weeks of intervention. In conclusion, oral intake of 100 mg/d liquid ubiquinol might benefit type 2 diabetes patients by increasing antioxidant enzyme activity levels, reducing HbA1c levels and maintaining HDL-cholesterol levels.

Quercetin enhances the antitumor effect of trichostatin A and suppresses muscle wasting in tumor-bearing mice.

Quercetin, a flavonol, displays anti-inflammatory and anti-cancer properties. This study aimed to investigate whether a diet containing 0.1% or 1% quercetin (LQ and HQ, respectively) enhances the anti-tumor effects of trichostatin A (TSA) and prevents muscle wasting induced by TSA. The positive control group received quercetin intraperitoneally (IQ). Three weeks after injecting A549 cells, nude mice were given TSA alone or in combination with quercetin administered orally or intraperitoneally for 16 weeks. Tumor volumes as well as body, muscle and epididymal fat weights were determined during or after the experiment. Quercetin given as a diet supplement dose-dependently enhanced the anti-tumor potency of TSA (p < 0.05). The enhancing effect of HQ was similar to that of IQ. HQ also significantly increased the expression of p53, a tumor suppressor, in tumor tissues compared with the TSA alone group. In addition, TSA-induced loss of gastrocnemius muscle weight was inhibited by oral quercetin in a dose dependent manner; the efficiencies of LQ and HQ were similar to or better than IQ. Moreover, both LQ and HQ decreased TSA-induced activation of Forkhead box O1 (FOXO1), a crucial transcription factor that regulates muscle wasting associated genes. Consistently, LQ and HQ suppressed muscle wasting associated proteins atrophy gene-1 and muscle ring-finger protein-1 expression as well as increased the myosin heavy chain level in the gastrocnemius muscles. Besides, quercetin attenuated TSA-increased oxidative damage and proinflammatory cytokines (p < 0.05). These findings demonstrate that a diet containing 0.1% or 1% quercetin enhances the antitumor effect of TSA and prevents TSA-induced muscle wasting.