Dioscin, one natural product, has various pharmacological actions. However, its effects on methotrexate (MTX)-induced hepatorenal damages still remain unknown. In the present study, the data ...manifested that dioscin restored the viabilities of L-02 and NRK-52E cells, reduced ALT, AST, Cr, BUN levels, and ameliorated histopathological changes of liver and kidney. Besides, dioscin decreased ROS levels in cells, and adjusted SOD, MDA, GSH and GSH-Px levels in rats. Dioscin reduced the expression levels of miR-145–5p which directly targeted Sirt5, and then regulated the expression levels of SOD1, Nrf2, Gst, Keap1, HO-1, GCLC and NQO1. MiR-145–5p mimic in cells deteriorated ROS levels and decreased Sirt5 expression to accentuate oxidative stress by regulating the expression levels of SOD1, Nrf2, Keap1, which were all reversed by dioscin. Moreover, MTX-induced hepatorenal damage were worsened in mice by Sirt5 siRNA or miR-145–5p agomir, which were also alleviated by dioscin. Dioscin relieved MTX-induced hepatorenal damages through regulating miR-145-5p-medicated oxidative stress, which should be considered as one effective drug to treat the disorder in future.
Proposed signaling mechanism of dioscin on restoring MTX-induced liver and kidney damages via regulating miR-145-5p-mediated oxidative stress. Dioscin up-regulated Sirt5 level by down-regulating miR-145–5p level to adjust the expression levels of Nrf2, HO-1, GCLC, NQO1, Gst, SOD1 and Keap1. Dioscin protected hepatorenal damages caused by MTX via regulating miR-145-5p-mediated oxidative stress. Display omitted
•Dioscin significantly relieved MTX-induced hepatorenal damages in vitro and in vivo.•MTX caused oxidative damages to the liver and kidney in vitro and in vivo.•miR-145–5p directly targeted Sirt5 to adjust oxidative stress.•Dioscin reduced the expression levels of miR-145–5p and suppressed w miR-145-5p-medicated oxidative stress.
Objectives
Supplementation of high protein oral nutrition shakes supplemented with β-hydroxy-β-methylbutyrate (HP-HMB) has been shown to improve muscle mass, muscle strength, and physical performance ...in older adults, but the roles of HP-HMB supplementation on the intramuscular adiposity remained unknown. This 12-week randomized controlled trial evaluated the changes of muscle mass, muscle strength, physical performance and intramuscular adiposity among community-dwelling pre-frail older persons.
Methods
This was an open-label, parallel group, randomized controlled trail that enrolled 70 community-dwelling pre-frail older persons without active or uncontrolled conditions, disability or dementia. The intervention group was provided with two services of HP HMB (Ensure® Plus Advance containing 3g HMB) per day for 12 weeks, and the control group was provided with professional nutritional counselling for sufficient protein intake. All participants received functional assessments, laboratory tests and magnetic resonance imaging (MRI) of the dominant leg before and after study. Intramuscular adipose tissue (IMAT) and the mid-thigh cross-sectional area (CSA) of muscle were obtained by MRI, and the IMAT-to-CSA ratio was calculated to evaluate intramuscular adiposity.
Results
Overall, 62 participants (mean age: 71.1±3.8 years, 69.4% female) completed the study (HP-HMB group: 29, control group: 33) and comparisons of baseline characteristics between groups were not statistically different. For the primary outcome, HP-HMB group showed significant improvements in the CSA of mid-thigh muscle (mean increase of CSA: 149.1±272.3 for HMB group vs −22.9±309.1 mm
2
for control group, P=0.045). The improvement of MNA-SF was borderline (0.28±0.75 vs. −0.15±0.94, P=0.064), but serum levels of Vit D were significantly increased in the HMB group (3.83±8.18 vs. −1.30±4.81 ng/mL, P=0.002). Moreover, the body weight and BMI were significantly increased in the HMB group (1.10±1.18 vs. 0.24±1.13 kg, P=0.005; 0.56±0.68 vs. 0.22±0.47 kg/m
2
, P=0.019). In particular, the IMAT-to-CSA ratio was reduced in the HMB group (−0.38±1.21 vs. −0.02±2.56 %, P=0.06). Using the generalized estimating equation, we found that SPPB score in chair rise test was significantly improved (β=0.71, 95% C.I.0.09–1.33, P=0.026).
Conclusions
The 12-week supplementation with high protein oral nutrition shake supplemented with 3g HMB per day significantly increased muscle mass, as well as nutritional status and physical performance, and ameliorated the intramuscular adiposity of pre-frail older persons. Further study is needed to explore the long-term benefits of HP-HMB supplementation on muscle and metabolic health for older adults.
OBJECTIVES: To evaluate the prevalence of malnutrition and its impact on mortality, functional decline and cognitive impairment among elder residents in long-term care settings. DESIGNS: A ...prospective cohort study. SETTINGS: Two veteran homes in Taiwan. PARTICIPANTS: A total of 1,248 male residents aged equal or more than 65 years. MEASUREMENTS: Charlson’s comorbidity index (CCI), Minimum data set (MDS), resident assessment protocols (RAP), Activity of daily living-Hierarchy scale, Cognitive Performance Scale, MDS Social engagement scale. RESULTS: The mean age of participants is 83.1 ± 5.1 years, and the prevalence of malnutrition was 6.1%. Inadequate dietary content (57.9%) and unintentional weight loss (31.6%) account for the majority of malnutrition identified by MDS tool. Higher 18-month mortality rate (25% vs. 14.2%), higher baseline CCI (median 1 vs. 0), and higher baseline sum of RAP triggers (median 8.5 vs. 5) were noted among residents with malnutrition. Furthermore, malnutrition was shown predictive for functional decline (OR: 3.096, 95% CI: 1.715-5.587) and potential cognitive improvement (OR: 2.469, 95% CI: 1.188-5.128) among survivors after adjustment for age, body mass index and CCI. CONCLUSION: Malnutrition among elder men residing in veteran homes was associated with multimoridities and higher care complexity, and was predictive for mortality and functional decline.
Objectives
To discern the diagnostic accuracy between the updated diagnostic consensus of the Asian Working Group for Sarcopenia (AWGS) in 2019 (AWGS 2019) and the previous AWGS 2014 guidelines.
...Design
A prospective population-based cohort study.
Setting and Participants
The study included 731 older community-dwelling adults aged ≥ 65 years who participated in face-to-face interviews and were followed up for 11-year mortality until 31 Mar 2022.
Measurements
We utilized a handgrip strength dynamometer to measure participants’ muscle strength, while their walking speed was determined by a timed 6-meter walk test at their usual pace. Additionally, muscle mass was measured using dual-energy X-ray absorptiometry scanning. Sarcopenia was defined as the presence of low muscle mass in combination with weakness and/or slowness both by AWGS 2014 and 2019 criteria.
Results
The present study followed 731 participants (mean age 73.4 ± 5.4 years, men predominant 52.8%) over a period of 11 years, yielding 5927 person-years and 159 deaths. Prevalence of sarcopenia defined by AWGS 2019 and 2014 criteria were 8.5% and 6.8%, respectively. Sarcopenia defined by AWGS 2019 (HR 1.62, 95% CI 1.04–2.54, p=0.034) but not AWGS 2014 was significantly associated with mortality in community-living older adults after adjusting for potential confounders such as age, sex, education, drinking, disease burden and serum level of testosterone. The study also found that the AWGS 2019 criteria had a better model fitness than AWGS 2014 criteria in predicting mortality.
Conclusion
AWGS 2019 criteria outperformed AWGS 2014 in identifying sarcopenia risk and predicting mortality. Screening for sarcopenia in older adults may improve health outcomes by identifying those at increased mortality risk.
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•HI/R injury significantly decreased the expression level of miR-142-3p.•miR-142-3p alleviated apoptosis and inflammation to relieve HI/R injury.•miR-142-3p directly targeted ...MARCKS.•MARCKS siRNA markedly inhibited HI/R injury.
MiR-142-3p as one key molecule in oncogenesis and inflammation plays crucial roles in hepatic fibrosis, hepatocellular carcinoma and other liver disease. However, there have no literatures to report its effects on hepatic ischemia-reperfusion (HI/R) injury. In the present work, hypoxia reoxygenation (H/R) models on AML12 and HepG2 cells, and ischemia/reperfusion model in mice were established. The methods of real-time PCR, dual luciferase reporter, mimic, inhibitor, agomir, antagomir and siRNA transfection assays were used. The expression levels of miR-142-3p were decreased in model groups in vitro and in vivo compared with control group or Sham group, which directly targeted MARCKS to regulate its expression. Then, MARCKS activated p38/JNK signal, up-regulated NF-κB expression to accelerate inflammation, and inhibited PI3K/AKT signal to promote apoptosis. Moreover, miR-142-3p mimic in vitro and agomir in vivo lowered the expression levels of MARCKS, thereby alleviating apoptosis and inflammation to relieve HI/R injury. Furthermore, miR-142- 3p inhibitor in vitro and antagomir in vivo up-regulated the expression levels of MARCKS to aggravate HI/R damage via promoting inflammation and apoptosis. Consistently, MARCKS siRNA markedly inhibited HI/R injury by restraining apoptosis and inflamm- ation in mice. MiR-142-3p played a considerable part in adjusting HI/R injury by targeting MARCKS, and miR-142-3p/MARCKS should be a new therapeutic target for HI/R injury.
Objectives
To evaluate the associations between cardiovascular disease (CVD) risk burden (estimated by the World Health Organization (WHO) algorithm) and cognitive impairments (e.g., incident ...dementia, global and domain-specific impairments) among CVD-, dementia- and disability-free, community-dwelling middle-aged and older adults during an 8-year follow-up.
Design
A community-based longitudinal cohort study.
Setting
Yuanshan township in Yi-Lan County, Taiwan.
Participants
A total of 889 community-dwelling residents aged 50 years or older.
Measurements
Age, sex, educational level, employment status, alcohol status, body mass index, physical activity, gait speed, depressive symptoms, WHO region-specific CVD risk scores (10-year CV risk, low: <10% vs. moderate-to-high: ≥ 10%), Chinese version of the Mini-Mental State Examination (MMSE), verbal memory by the delay-free recall in the Chinese Version Verbal Learning Test (CVVLT), language function by the Boston Naming Test and the category (animal) Verbal Fluency Test, visuospatial function by the Taylor Complex Figure Test, executive function by the digit backward and the Clock Drawing Test.
Results
Compared to those with low CVD risk, middle-aged and older adults with moderate-to-high CVD risk were at greater risk for cognitive impairments with respect to the MMSE (adjusted odds ratio (aOR) 1.60 95% confidence interval (CI) 1.19–2.15, P=0.002), verbal memory (aOR 1.97 1.43-2.70, P< 0.001) and language (aOR 1.99 1.46–2.70, P< 0.001), as well as incident dementia (aOR 2.40 1.33–4.33, P=0.004). After adjusting for all covariates, CVD risk was not associated with other domains of cognitive impairment.
Conclusions
Among healthy, community-dwelling, middle-aged and older adults, those with moderate-to-high cardiovascular risk burden were significantly associated with incident dementia and global and domain-specific cognitive impairments (verbal memory and language), which suggests the existence of a relationship between early cognitive deficits and CVD risk burden. Further studies are needed to elucidate the pathophysiological mechanism of the link between CVD risk burden and cognitive impairment.
BACKGROUND: Although metabolic syndrome (MetS) has been reported to be associated with cognitive decline and dementia, little was known about late-life MetS and cognitive decline among older old ...population. The main purpose of this study was to evaluate the role of MetS and cognitive decline among men aged 75 and over in Taiwan. METHODS: This is a prospective cohort study which recruited men aged 75 years and older with intact cognitive function living in the Banciao Veterans Home, a retirement community for veterans in northern Taiwan. All participants received complete history taking, physical examinations, global cognitive tests and laboratory tests. Cognitive status was re-evaluated one year after enrollment to evaluate the role of MetS to cognitive decline in this study population. RESULTS: Overall, 338 people participated in the study and 62 of them were excluded due to low baseline MMSE score, and the remaining 276 people (mean age: 82.4±4.2 years) were enrolled for study. The prevalence of MetS and annual cognitive decline were 22.5% and 15.6%, respectively. During the follow-up period, 9 (3.3%) participants died, 229(83.0%) complete the study. Subjects with cognitive decline were older and had lower serum levels of serum total cholesterol. Multivariate logistic regression showed that older age (OR:1.13, 95% C.I.: 1.01–1.25, P=0.026) and central obesity (OR: 4.19, 95% CI: 1.26–13.91, P=0.019) were independent risk factors for cognitive decline; and MetS defined by Adult Treatment Panel III was a protective factor (OR: 0.20, 95% CI: 0.04–0.94, P=0.041). The protective effect of MetS remained the same when MetS was defined by the criteria of International Diabetes Federation. CONCLUSIONS: Age and central obesity were significant risk factors of cognitive decline, but late-life MetS, however defined, had protective effect on cognitive function. Further investigation is needed to clarify the possible mechanism of MetS and cognitive function in older adults.
Sewage-based epidemiology was applied for the first time to a number of mainland Chinese megacities. The application monitored influents to 9 sewage treatment plants (STPs) to estimate the use of ...illicit drugs in Beijing, Guangzhou, Shenzhen, and Shanghai. Altogether, 11.4million inhabitants were covered during September–October 2012. 24-h composite raw sewage samples were collected for 4 consecutive days at each STP. Each collected sample was analyzed for cocaine, benzoylecgonine, ecgonine methylester, methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, 6-monoacetylmorphine, amphetamine, methamphetamine, ecstasy, mephedrone, methylenedioxypyrovalerone, 11-nor-9-carboxy-delta-9-tetrahydrocannabinol, ketamine, and norketamine. Through the analysis of these chemical residues, the use of amphetamine, cannabis, cocaine, ecstasy, heroin, mephedrone, methadone, methamphetamine, methylenedioxypyrovalerone and ketamine among Chinese urban inhabitants was monitored. The results obtained demonstrated in a quantitative way that the drug use patterns of Chinese are different from their European counterparts. Abuse of methamphetamine and ketamine was particularly noteworthy in China, while consumption of cocaine and ecstasy, the most popular drugs in Europe, was very low among the sampled Chinese inhabitants. Further, the use of most drugs demonstrated a geographical trend, since their use was much higher in the southern cities of Shenzhen and Guangzhou than it was in Beijing and Shanghai. Interestingly, the exclusive, but minor, metabolite of heroin, 6-monoacetylmorphine, was detected only sporadically. This would suggest that the use of heroin among Chinese urban users sampled in the study was low. Further, the patterns of drug use observed during the study are largely consistent with trends reported by the United Nations Office on Drugs and Crime. Overall, our study suggests that sewage-based epidemiology can readily be used to monitor the use of illicit drugs in those countries/regions where traditional means to monitor drug use patterns have only yielded limited or information of questionable reliability.
•First study on sewage-based epidemiology in megacities from mainland China.•Higher consumption of methamphetamine, ecstasy, ketamine and cocaine in South compared to North.•Omnipresent use of methamphetamine among cities of mainland China.•Prevalent use of ketamine in Southern China.•Influent loads of most drugs were consistent with trends reported by the UNODC.
Our previous study revealed that microRNA-125a-5p plays a crucial role in regulating hepatic glycolipid metabolism by targeting STAT3 in type 2 diabetes mellitus (T2DM). Dioscin, a major active ...ingredient in Dioscoreae nipponicae rhizomes, displays various pharmacological activities, but its role in T2DM has not been reported.
The aim of this study was to investigate the effect of dioscin on T2DM and elucidate its potential mechanism.
The effect of dioscin on glycolipid metabolic disorder in insulin-induced HepG2 cells, palmitic acid-induced AML12 cells, high-fat diet- and streptozotocin- induced T2DM rats, and spontaneous T2DM KK-Ay mice were evaluated. Then, the possible mechanisms of dioscin were comprehensively evaluated.
Dioscin markedly alleviated the dysregulation of glycolipid metabolism in T2DM by reducing hyperglycemia and hyperlipidemia, improving insulin resistance, increasing hepatic glycogen content, and attenuating lipid accumulation. When the mechanism was investigated, dioscin was found to markedly elevate miR-125a-5p level and decrease STAT3 expression. Consequently, dioscin increased phosphorylation levels of STAT3, PI3K, AKT, GSK-3β, and FoxO1 and decreased gene levels of PEPCK, G6Pase, SREBP-1c, FAS, ACC, and SCD1, leading to an increase in glycogen synthesis and a decrease in gluconeogenesis and lipogenesis. The effects of dioscin on regulating miR-125a-5p/STAT3 pathway were verified by miR-125a-5p overexpression and STAT3 overexpression.
Dioscin showed potent anti-T2DM activity by improving the inhibitory effect of miR-125a-5p on STAT3 signaling to alleviate glycolipid metabolic disorder of T2DM.
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