Limited microRNAs (miRNAs, miRs) have been reported to be necessary for exercise-induced cardiac growth and essential for protection against pathological cardiac remodeling. Here we determined members of the miR-17-92 cluster and their passenger miRNAs expressions in two distinct murine exercise models and found that miR-17-3p was increased in both. miR-17-3p promoted cardiomyocyte hypertrophy, proliferation, and survival. TIMP-3 was identified as a direct target gene of miR-17-3p whereas PTEN was indirectly inhibited by miR-17-3p. Inhibition of miR-17-3p in vivo attenuated exercise-induced cardiac growth including cardiomyocyte hypertrophy and expression of markers of myocyte proliferation. Importantly, mice injected with miR-17-3p agomir were protected from adverse remodeling after cardiac ischemia/reperfusion injury. Collectively, these data suggest that miR-17-3p contributes to exercise-induced cardiac growth and protects against adverse ventricular remodeling. miR-17-3p may represent a novel therapeutic target to promote functional recovery after cardiac ischemia/reperfusion.
Background and Purpose— To determine the effect of a multifaceted stroke telerehabilitation (STeleR) intervention on physical function, and secondarily on disability, in veterans poststroke. Methods— We conducted a prospective, randomized, multisite, single-blinded trial in 52 veterans with stroke from 3 Veterans Affairs medical centers. Veterans with a stroke in the preceding 24 months were randomized to the STeleR intervention or usual care. The STeleR intervention consisted of 3 home visits, 5 telephone calls, and an in-home messaging device provided over 3 months to instruct patients in functionally based exercises and adaptive strategies. Usual care participants received routine rehabilitation care as prescribed by their physicians. The primary outcome measures were improvement in function at 6 months, measured by both the motor subscale of the Telephone Version of Functional Independence Measure and by the function scales of the Late-Life Function and Disability Instrument. Results— The 2 complementary primary outcomes (Late-Life Function and Disability Instrument Function and Telephone Version of Functional Independence Measure) improved at 6 months for the STeleR group and declined for the usual care group, but the differences were not statistically significant ( P =0.25, Late-Life Function and Disability Instrument; P =0.316). Several of secondary outcomes were statistically significant. At 6 months, compared with the usual care group, the STeleR group showed statistically significant improvements in 4 of the 5 Late-Life Function and Disability Instrument disability component subscales ( P <0.05), and approached significance in 1 of the 3 Function component subscales ( P =0.06). Conclusions— The STeleR intervention significantly improved physical function, with improvements persisting up to 3 months after completing the intervention. STeleR could be a useful supplement to traditional poststroke rehabilitation given the limited resources available for in-home rehabilitation for stroke survivors. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00384748.
Recent studies have suggested that undernutrition as defined using multidimensional nutritional evaluation tools may affect clinical outcomes in heart failure (HF). The evidence supporting this correlation is unclear. Therefore, we conducted this systematic review to critically appraise the use of multidimensional evaluation tools in the prediction of clinical outcomes in HF. We performed descriptive analyses of all identified articles involving qualitative analyses. We used STATA to conduct meta-analyses when at least three studies that tested the same type of nutritional assessment or screening tools and used the same outcome were identified. Sensitivity analyses were conducted to validate our positive results. We identified 17 articles with qualitative analyses and 11 with quantitative analysis after comprehensive literature searching and screening. We determined that the prevalence of malnutrition is high in HF (range 16-90 %), particularly in advanced and acute decompensated HF (approximate range 75-90 %). Undernutrition as identified by multidimensional evaluation tools may be significantly associated with hospitalization, length of stay and complications and is particularly strongly associated with high mortality. The meta-analysis revealed that compared with other tools, Mini Nutritional Assessment (MNA) scores were the strongest predictors of mortality in HF [HR (4.32, 95 % CI 2.30-8.11)]. Our results remained reliable after conducting sensitivity analyses. The prevalence of malnutrition is high in HF, particularly in advanced and acute decompensated HF. Moreover, undernutrition as identified by multidimensional evaluation tools is significantly associated with unfavourable prognoses and high mortality in HF.
Mulberry (Morus alba L.) belongs to the Moraceae family and is widely planted in Asia. Mulberry fruits are generally consumed as fresh fruits, jams and juices. They contain considerable amounts of biologically active ingredients that might be associated with some potential pharmacological activities that are beneficial for health. Therefore, they have been traditionally used in traditional medicine. Studies have reported that the presence of bioactive components in mulberry fruits, including alkaloids and flavonoid, are associated with bioactivities such as antioxidant. One of the most important compounds in mulberry fruits is anthocyanins which are water-soluble bioactive ingredients of the polyphenol class. Studies have shown that mulberry fruits possess several potential pharmacological health benefits including anti-cholesterol, anti-obesity and hepatoprotective effects which might be associated with the presence of some of these bioactive compounds. However, human intervention studies on the pharmacological activities of mulberry fruits are limited. Therefore, future studies should explore the effect of mulberry fruit consumption on human health and elucidate the detailed compounds. This paper provides an overview of the pharmacological activities of mulberry fruits.
Dysregulation of microRNAs has been implicated in many cardiovascular diseases including fibrosis. Here we report that miR-433 was consistently elevated in three models of heart disease with prominent cardiac fibrosis, and was enriched in fibroblasts compared to cardiomyocytes. Forced expression of miR-433 in neonatal rat cardiac fibroblasts increased proliferation and their differentiation into myofibroblasts as determined by EdU incorporation, α-SMA staining, and expression levels of fibrosis-associated genes. Conversely, inhibition of miR-433 exhibited opposite results. AZIN1 and JNK1 were identified as two target genes of miR-433. Decreased level of AZIN1 activated TGF-β1 while down-regulation of JNK1 resulted in activation of ERK and p38 kinase leading to Smad3 activation and ultimately cardiac fibrosis. Importantly, systemic neutralization of miR-433 or adeno-associated virus 9 (AAV9)-mediated cardiac transfer of a miR-433 sponge attenuated cardiac fibrosis and ventricular dysfunction following myocardial infarction. Thus, our work suggests that miR-433 is a potential target for amelioration of cardiac fibrosis.
SummaryWe determined the effect of a multifaceted stroke telerehabilitation (STeleR) intervention on fallsrelated self-efficacy and satisfaction with care. We conducted a prospective, randomized, multisite, single-blinded trial in 52 veterans from three Veterans Affairs Medical Centers. Participants who experienced a stroke in the past 24 months were randomized to the STeleR Reprints and permissions: sagepub.co.uk/journalsPermissions.nav
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