Effect of stimuli type on affective memory of patients with different severities of cognitive impairment.

OBJECTIVES: To understand the differences in affective memory performance under different degrees of cognitive impairment, this study recruited older people with different degrees of cognitive impairment, to perform emotion recognition memory tasks. METHODS: Fifty-four elderly participants aged (65-85 years) were recruited. Of these, 18 had mild cognitive impairment, 18 had a mild form of Alzheimer's disease, and the remaining 18 were healthy. Factors such as the different emotional valences (positive, neutral, or negative) and stimulus types (pictures, words, or sounds) were manipulated to explore their influences on the emotion recognition memory of people with different degrees of cognitive impairment. RESULTS: The results showed that people's performance to positive stimuli worsened as their degree of cognitive impairment increased. All participants had difficulty processing memory of affective sound stimuli compared to the other two stimulus types. CONCLUSIONS: The results explain the decline in the cognitive ability process, in affective memory performance, of people with different degrees of cognitive impairment. This abnormal decline on affective memory performance could be an early diagnostic indicator of Alzheimer's disease. The results can hopefully be used as a reference for subsequent research on cognition-related diseases and age-related decline, especially regarding affective memory.

Flexural Strengthening of Large-Scale RC Beams with Nonprestressed and Prestressed CFRP Using Different Anchorages.

Externally bonded carbon-fiber-reinforced polymer (CFRP) technology can be used by different methods based on the anchorage device, CFRP type, and prestressing/nonprestressing. However, a direct comparison between the strengthening efficacies of different methods is still lacking. Seven large-scale RC beams were tested in this study to investigate the influences of the anchorage method, CFRP type, prestress, and prestressing system on the flexural strengthening efficacy of RC beams. The test results showed that the ultimate load increased by 38.3%, whereas the cracking and yielding loads were slightly affected when the anchorage method was enhanced from CFRP U-wraps to wedge-clamp anchors. The CFRP plate and CFRP sheet could provide a rather close flexural strengthening efficacy under the same CFRP strengthening amount. Compared to the nonprestressed CFRP plate, the prestressed CFRP plate was highly superior in improving the flexural behavior of RC beams. The cracking, yielding, and ultimate loads of the prestressed CFRP-strengthened specimens were 57.1%, 22.9%, and 5.9%, respectively, higher than those of the nonprestressed CFRP-strengthened specimen with an effective anchorage. The two types of prestressing systems based on the adhesive-friction anchor and wedge-clamp anchor were proven to be effective for flexural strengthening of RC beams with prestressed CFRP plates, and they could provide almost the same strengthening effect.

RNA sequencing reveals novel LncRNA/mRNAs co-expression network associated with puerarin-mediated inhibition of cardiac hypertrophy in mice.

Background: Evidence has demonstrated that puerarin is a potential medicine for the treatment of cardiac hypertrophy. However, the precise underlying molecular mechanisms of the protective effect of puerarin are still unclear. Here, we aimed to explore the regulatory mechanisms of lncRNAs/mRNAs co-expression network in a cardiac hypertrophy mouse model after puerarin treatment. Methods: A mouse model of cardiac hypertrophy was established by transverse aortic constriction (TAC). The echocardiography, tissue staining and western blot were used to examine the protective effect of puerarin. Then RNA sequencing (RNA-seq) was carried out to analyze systematically mRNAs and lncRNAs expression. The target lncRNA were confirmed using qRT-PCR. Moreover, a coding/non-coding gene co-expression network were established to find the interaction of lncRNA and mRNAs. The biological process, cellular component, molecular function and pathways of different expression mRNAs targeted by lncRNA were explored using Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis. Results: Puerarin exhibited an obvious inhibitory effect in cardiac hypertrophy in TAC model. RNA-seq analysis was performed to investigate the lncRNAs and mRNAs expression patterns of cardiomyocytes in sham and TAC groups treated with or without puerarin. RNA-seq identified that TAC downregulated four lncRNAs, which could be revised by puerarin treatment (|log2 Fold change| > 2 and FDR < 0.05). Among them, expression alterations of lncRNA Airn (antisense of Igf2r non-protein coding RNA) was confirmed by qRT-PCR. Pearson's correlation coefficients of co-expression levels suggested that there was an interactive relationship between Airn and 2,387 mRNAs (r > 0.95 or r < -0.95). Those co-expressed mRNAs were enriched in some important biological processes such as translational initiation, cell proliferation, insulin-like growth factor binding and poly(A) RNA binding. KEGG analyses suggested that those Airn-interacted mRNAs were enriched in endocytosis, signaling pathways regulating pluripotency of stem cells and the Jak-STAT pathway. Conclusion: Puerarin may exert beneficial effects on cardiac hypertrophy through regulating the lncRNAs/mRNAs co-expression network.

Role of stimulus types and valence on the affective memory performance of adults with anxiety.

Previous studies have found that the emotion of anxiety in adults is easily influence by negative stimuli However, few studies have explored the effect of stimulus types on working memory performance and cognitive processing of adults with anxiety. This study aimed to explore the effects of anxiety on affective working memory and the role of stimulus types and valences on affective working memory performance. Forty adults were recruited for the experiment and were divided into two groups according to their anxiety levels. The valence and type of stimulus were manipulated in a memory recognition experiment. The results indicated that individuals with anxiety performed poorer when subjected to positive stimuli than for neutral and negative stimuli, whereas healthy adults exhibited the opposite. Furthermore, participants outperformed on affective pictures than affective words, but the effect size of the words was larger than that of the pictures for the difference between the valence and anxiety groups. This study highlights the differences in affective working performance across stimulus types and valences between healthy adults and adults with anxiety. The findings clarified the effect of positive valence and affective words on the affective working memory processing mechanism in adults with anxiety.

Afterload-related cardiac performance identifies cardiac impairment and associates with outcome in patients with septic shock: a retrospective cohort study.

BACKGROUND: Septic patients with cardiac impairment are with high mortality. Afterload-related cardiac performance (ACP), as a new tool for diagnosing septic cardiomyopathy (SCM), still needs to be evaluated for its impact on the prognosis for patients with septic shock. METHODS: In this retrospective study, 100 patients with septic shock undertaken PiCCO monitoring were included. The ability of ACP, cardiac index (CI), and cardiac power index (CPI) to discriminate between survivors and non-survivors was tested by comparing the area under the receiver operating characteristic curve (AUROC) analysis. Cox proportional hazards regression analyses were performed to assess the associations of ACP with day-28 mortality. Curve estimation was used to describe the relationship between the hazard ratio (HR) of death and ACP. RESULTS: ACP had a strong linear correlation with CI and CPI (P < 0.001). ACP demonstrated significantly greater discrimination for day-28 mortality than CI before adjusted [AUROC 0.723 (95% CI 0.625 to 0.822) vs. 0.580 (95% CI 0.468 to 0.692), P = 0.007] and CPI after adjusted [AUROC 0.693 (95% CI 0.590 to 0.797) vs. 0.448 (0.332 to 0.565), P < 0.001]. Compared with ACP > 68.78%, HR for ACP ≤ 68.78% was 3.55 (1.93 to 6.54) (P < 0.001). When adjusted with age, APACHE-II score, Vasoactive Inotropic Score, Lactate, CRRT, day-1 volume, fibrinogen and total bilirubin as possible confounders, and decrease ACP are still associated with increasing day-28 mortality (P < 0.05). An exponential relationship was observed between ACP12h and HR of day-28 death. CONCLUSIONS: Our results suggested thatACP could improve mortality predictions when compared to CI and CPI. Decreased ACP was still an independent risk factor for increased day-28 mortality.

Puerarin ameliorated pressure overload-induced cardiac hypertrophy in ovariectomized rats through activation of the PPARα/PGC-1 pathway.

Estrogen deficiency induces cardiac dysfunction and increases the risk of cardiovascular disease in postmenopausal women and in those who underwent bilateral oophorectomy. Previous evidence suggests that puerarin, a phytoestrogen, exerts beneficial effects on cardiac function in patients with cardiac hypertrophy. In this study, we investigated whether puerarin could prevent cardiac hypertrophy and remodeling in ovariectomized, aortic-banded rats. Female SD rats subjected to bilateral ovariectomy (OVX) plus abdominal aortic constriction (AAC). The rats were treated with puerarin (50 mg·kg-1 ·d-1, ip) for 8 weeks. Then echocardiography was assessed, and the rats were sacrificed, their heart tissues were extracted and allocated for further experiments. We showed that puerarin administration significantly attenuated cardiac hypertrophy and remodeling in AAC-treated OVX rats, which could be attributed to activation of PPARα/PPARγ coactivator-1 (PGC-1) pathway. Puerarin administration significantly increased the expression of estrogen-related receptor α, nuclear respiratory factor 1, and mitochondrial transcription factor A in hearts. Moreover, puerarin administration regulated the expression of metabolic genes in AAC-treated OVX rats. Hypertrophic changes could be induced in neonatal rat cardiomyocytes (NRCM) in vitro by treatment with angiotensin II (Ang II, 1 µM), which was attenuated by co-treatemnt with puerarin (100 µM). We further showed that puerarin decreased Ang II-induced accumulation of non-esterified fatty acids (NEFAs) and deletion of ATP, attenuated the Ang II-induced dissipation of the mitochondrial membrane potential, and improved the mitochondrial dysfunction in NRCM. Furthermore, addition of PPARα antagonist GW6471 (10 µM) partially abolished the anti-hypertrophic effects and metabolic effects of puerarin in NRCM. In conclusion, puerarin prevents cardiac hypertrophy in AAC-treated OVX rats through activation of PPARα/PGC-1 pathway and regulation of energy metabolism remodeling. This may provide a new approach to prevent the development of heart failure in postmenopausal women.

Puerarin Alleviates Lipopolysaccharide-Induced Myocardial Fibrosis by Inhibiting PARP-1 to Prevent HMGB1-Mediated TLR4-NF-κB Signaling Pathway.

Myocardial fibrosis (MFs) is a crucial pathological process that results in cardiac failure in the development of multiple cardiovascular diseases. Puerarin could reportedly be used to treat a variety of cardiovascular diseases. However, the exact mechanism of puerarin on MFs was not clear enough. The separated primary cardiac fibroblasts (CFs) were induced by lipopolysaccharide (LPS) and treated with puerarin. The levels of TNF-α, IL-6, HMGB1, PARP-1, α-SMA, collagen-1, collagen-3, NF-κB pathways were examined by ELISA, immunofluorescence, RT-qPCR, western blot and immunohistochemistry assays. In addition, MFs rats' model was established using transverse aortic constriction (TAC), and the degree of fibrosis was certified by masson staining. We successfully separated primary CFs, and certified that LPS induction could upregulate the levels of PARP-1, HMGB1, inflammatory cytokines and fibrosis-related proteins (α-SMA, collagen-1 and collagen-3). In addition, we proved that puerarin could weaken MFs, and PARP-1 and HMGB1 expressions, which were induced by LPS in primary CFs. In terms of mechanism, HMGB1 expression could be promoted by PARP-1, and PARP-1 could attenuate the therapeutic effect of puerarin on LPS-induced MFs. Besides, PARP-1-HMGB1-NF-κB pathway was related to the protective effect of puerarin on MFs. In vivo, we also verified the protective efficacy of puerarin on MFs induced by TAC, and puerarin also regulated HMGB1-mediated TLR4-NF-κB signaling pathway. We demonstrated that puerarin could ameliorate MFs by downregulating PARP-1 to inhibit HMGB1-mediated TLR4-NF-κB signaling pathway in LPS-induced primary CFs and TAC-induced MFs rats' model.

Effect of puerarin on action potential and sodium channel activation in human hypertrophic cardiomyocytes.

OBJECTIVE: To study the effect of puerarin on electrophysiology using a hypertrophic cardiomyocyte (HC) model. MATERIALS AND METHODS: Human urine epithelial cells were used to generate the HC model (hiPSC-CM). Cardiomyocyte hypertrophy was induced by applying 10 nM endothelin-1 (ET-1). Effects of puerarin pre-treatment (PPr) and post-treatment (PPo) on action potential, sodium current (INa) activation and inactivation, and recovery following INa inactivation were tested using patch clamp electrophysiology. RESULTS: Depolarization to repolarization 50% time (APD50) and repolarization 30% time (APD30) were significantly prolonged in the PPo and PPr groups compared with the controls. However, there were no significant differences in the action potential depolarization amplitude (APA) or the maximum depolarization velocity (Vmax) in phase 0. The PPr group had a slightly shortened APD90, and an extended APD50 and APD30, but did not exhibit any significant changes in stage A of APA and Vmax. The PPo group did not exhibit any significant changes in INa, while 12 h of PPr improved INa. However, puerarin did not significantly affect the activation, inactivation, or recovery of the sodium channel. CONCLUSIONS: Cardiomyocyte hypertrophy significantly decreased the Vmax of the action potential and the peak density of INa. PPr inhibited the decrease in Vmax and increased the peak density of INa. Thus, puerarin could be used to stabilize the electrophysiological properties of hypertrophic cardiomyocytes and reduce arrhythmias.

Memory Performance of People with Different Dementia Severity for Different Semantic Hierarchies.

BACKGROUND: Memory disorder is a significant symptom during early-stage Alzheimer's disease (AD). Changes in semantic memory are frequently seen in terms of forgetting names, loss of word meanings, and difficulties in linguistic expression. Significant semantic degeneration is not a normal phenomenon in elderly persons, and it may be an important sign in the early stages of progression of AD. METHODS: Thirty-four participants aged between 60 and 86 years were recruited for an experiment with a 3 × 4 × 2 factorial design that was conducted to explore the differences in semantic memory performance among controls with normal cognitive performance (NC), individuals classified as mildly cognitively impaired (MCI), and individuals with AD. RESULTS: The performance of participants diagnosed with mild AD was poorest for the attribute category, and there was no difference in response to different word frequencies. Although those diagnosed with MCI performed similarly to healthy elderly participants in terms of semantic memory, their performance profiles for different semantic hierarchies were similar to those of participants with AD. CONCLUSION: Semantic memory had degraded among participants with AD and MCI, and the rate of semantic degeneration was different in different semantic hierarchies.

Contributions of Nrf2 to Puerarin Prevention of Cardiac Hypertrophy and its Metabolic Enzymes Expression in Rats.

Previous evidence has suggested that puerarin may attenuate cardiac hypertrophy; however, the potential mechanisms have not been determined. Moreover, the use of puerarin is limited by severe adverse events, including intravascular hemolysis. This study used a rat model of abdominal aortic constriction (AAC)-induced cardiac hypertrophy to evaluate the potential mechanisms underlying the attenuating efficacy of puerarin on cardiac hypertrophy, as well as the metabolic mechanisms of puerarin involved. We confirmed that puerarin (50 mg/kg per day) significantly attenuated cardiac hypertrophy, upregulated Nrf2, and decreased Keap1 in the myocardium. Moreover, puerarin significantly promoted Nrf2 nuclear accumulation in parallel with the upregulated downstream proteins, including heme oxygenase 1, glutathione transferase P1, and NAD(P)H:quinone oxidoreductase 1. Similar results were obtained in neonatal rat cardiomyocytes (NRCMs) treated with angiotensin II (Ang II; 1 µM) and puerarin (100 µM), whereas the silencing of Nrf2 abolished the antihypertrophic effects of puerarin. The mRNA and protein levels of UGT1A1 and UGT1A9, enzymes for puerarin metabolism, were significantly increased in the liver and heart tissues of AAC rats and Ang II-treated NRCMs. Interestingly, the silencing of Nrf2 attenuated the puerarin-induced upregulation of UGT1A1 and UGT1A9. The results of chromatin immunoprecipitation-quantitative polymerase chain reaction indicated that the binding of Nrf2 to the promoter region of Ugt1a1 or Ugt1a9 was significantly enhanced in puerarin-treated cardiomyocytes. These results suggest that Nrf2 is the key regulator of antihypertrophic effects and upregulation of the metabolic enzymes UGT1A1 and UGT1A9 of puerarin. The autoregulatory circuits between puerarin and Nrf2-induced UGT1A1/1A9 are beneficial to attenuate adverse effects and maintain the pharmacologic effects of puerarin.

Nrf2 Is a Key Regulator on Puerarin Preventing Cardiac Fibrosis and Upregulating Metabolic Enzymes UGT1A1 in Rats.

Puerarin is an isoflavone isolated from Radix puerariae. Emerging evidence shown that puerarin possesses therapeutic benefits that aid in the prevention of cardiovascular diseases. In this study, we evaluated the effects of puerarin on oxidative stress and cardiac fibrosis induced by abdominal aortic banding (AB) and angiotensin II (AngII). We also investigated the mechanisms underlying this phenomenon. The results of histopathological analysis, as well as measurements of collagen expression and cardiac fibroblast proliferation indicated that puerarin administration significantly inhibited cardiac fibrosis induced by AB and AngII. These effects of puerarin may reflect activation of Nrf2/ROS pathway. This hypothesis is supported by observed decreases of reactive oxygen species (ROS), decreases Keap 1, increases Nrf2 expression and nuclear translocation, and decreases of collagen expressions in cardiac fibroblasts treated with a combination of puerarin and AngII. Inhibition of Nrf2 with specific Nrf2 siRNA or Nrf2 inhibitor brusatol attenuated anti-fibrotic and anti-oxidant effects of puerarin. The metabolic effects of puerarin were mediated by Nrf2 through upregulation of UDP-glucuronosyltransferase (UGT) 1A1. The Nrf2 agonist tBHQ upregulated protein expression of UGT1A1 over time in cardiac fibroblasts. Treatment with Nrf2 siRNA or brusatol dramatically decreased UGT1A1 expression in puerarin-treated fibroblasts. The results of chromatin immunoprecipitation-qPCR further confirmed that puerarin significantly increased binding of Nrf2 to the promoter region of Ugt1a1. Western blot analysis showed that puerarin significantly inhibited AngII-induced phosphorylation of p38-MAPK. A specific inhibitor of p38-MAPK, SB203580, decreased collagen expression, and ROS generation induced by AngII in cardiac fibroblast. Together, these results suggest that puerarin prevents cardiac fibrosis via activation of Nrf2 and inactivation of p38-MAPK. Nrf2 is the key regulator of anti-fibrotic effects and upregulates metabolic enzymes UGT1A1. Autoregulatory circuits between puerarin and Nrf2-regulated UGT1A1 attenuates side effects associated with treatment, but it does not weaken puerarin's pharmacological effects.

Puerarin-7-O-glucuronide, a water-soluble puerarin metabolite, prevents angiotensin II-induced cardiomyocyte hypertrophy by reducing oxidative stress.

This study aimed to investigate the anti-oxidant and anti-hypertrophic effects of puerarin-7-O-glucuronide, a water-soluble puerarin metabolite. The anti-oxidant effects of puerarin-7-O-glucuronide were assessed by measurement of intracellular superoxide levels, total superoxide dismutase (SOD) activity, total anti-oxidant capacity, and glutathione (GSH)/glutathione disulfide (GSSG) ratio in cultured neonatal rat cardiomyocytes (NRCMs) stimulated with the xanthine oxidase (XO)/xanthine (X) system or angiotensin II. The activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and expression of NADPH oxidase subunits p22phox and p47phox were determined. The anti-hypertrophic effects of puerarin-7-O-glucuronide in angiotensin II-challenged NRCMs were characterized by changes in cell morphology and expression of hypertrophic genes. In the pharmacokinetic study, the plasma concentration of puerarin-7-O-glucuronide was determined by rapid resolution-liquid chromatography-tandem mass spectrometry (RR-LC-MS/MS). Puerarin-7-O-glucuronide prevented XO/X-induced increase in intracellular superoxide production and decreases in total SOD activity, GSH/GSSG ratio, and total anti-oxidant capacity. Puerarin-7-O-glucuronide also reversed angiotensin II-induced increases in intracellular superoxide production and NADPH oxidase activity and decreases in total SOD activity. These anti-oxidant effects of puerarin-7-O-glucuronide were accompanied by downregulation of p22phox and p47phox. Furthermore, puerarin-7-O-glucuronide prevented angiotensin II-induced increases in cell surface area and perimeter, as well as changes in Nppa, Myh7, and Myh6. In the pharmacokinetic study, puerarin-7-O-glucuronide was cleared with a half-life of 0.94 h after intravenous administration. Puerarin could be detected in rat plasma, albeit in low concentration, as early as 5 min after intravenous administration of puerarin-7-O-glucuronide. These anti-oxidant and anti-hypertrophic properties of puerarin-7-O-glucuronide were similar to those of its parent compound puerarin. These results support the development of puerarin-7-O-glucuronide as a novel pharmaceutical agent for therapeutic application.

Impact of Timing following Acute Myocardial Infarction on Efficacy and Safety of Bone Marrow Stem Cells Therapy: A Network Meta-Analysis.

Background. The optimal timing for Bone Marrow Stem Cells (BMCs) therapy following acute myocardial infarction (AMI) remains unclear. Aims. To synthesize the evidence from trials using a multiple-treatment comparison method, thereby permitting a broader comparison across multiple timing of BMCs therapy. Methods and Results. Randomized controlled trials in patients with AMI receiving BMCs therapy were identified from PubMed, Ovid LWW, BIOSIS Previews, and the Cochrane Library through January 2015. 2 035 patients of 31 studies included in our analysis were allocated to 5 groups' treatments: 1~3 days, 4~7 days, 8~14 days, 15~30 days, or placebo/control group. The multiple-treatment meta-analysis showed that 4~7 days' group could lead to significantly increased left ventricular ejection fraction (LVEF) as compared with control (mean of MDs and 95% CI: 6 months, 3.05 (0.92~5.25); 12 months, 4.18 (2.30~5.84)). Only 4~7 days led to significant reduction of MACEs compared with control (OR and 95% CI 0.34 (0.13~0.96)) for 12-months follow-up. In simulated comparisons, the 4~7 days' group ranked better than other timing groups for improvement of LVEF or reduction of the incidence of major adverse cardiac events. Conclusions. 4~7 days after AMI might be the optimal timing for cell therapy in terms of efficacy or safety.

C-reactive protein stimulates RAGE expression in human coronary artery endothelial cells in vitro via ROS generation and ERK/NF-κB activation.

AIM: The receptor for advanced glycation end-products (RAGE) plays an important role in development of atherosclerosis, and C-reactive protein (CRP) has been found to stimulate its expression in endothelial cells. In this study we investigated how CRP regulated the expression of RAGE in human coronary artery endothelial cells (HCAECs). METHODS: HCAECs were treated in vitro with CRP (50 µg/mL) in combination with a variety of inhibitors. ROS generation was determined by immunocytochemistry and flow cytometry. The RAGE expression and phosphorylation of relevant signaling proteins were measured using Western blot analyses. RESULTS: CRP stimulated the expression of RAGE in the cells, accompanied by markedly increased ROS generation, phosphorylation of ERK1/2 and NF-κB p65, as well as translocation of NF-κB p65 to the nuclei. CRP also stimulated phosphorylation of JNK and p38 MAPK. Pretreatment of the cells with the ROS scavenger N-acetyl-L-cysteine, ERK inhibitor PD98059 or NF-κB inhibitor PDTC blocked CRP-stimulated RAGE expression, but pretreatment with the NADPH oxidase inhibitor DPI, JNK inhibitor SP600125 or p38 MAPK inhibitor SB203580 did not significantly alter CRP-stimulated RAGE expression. CONCLUSION: CRP stimulates RAGE expression in HCAECs in vitro via ROS generation and activation of the ERK/NF-κB signaling pathway.

Effectiveness and safety of selected bone marrow stem cells on left ventricular function in patients with acute myocardial infarction: a meta-analysis of randomized controlled trials.

BACKGROUND: Concerns regarding the use of selected bone marrow stem cells (BMSCs) in the field of cardiac repair after acute ischemic events have been raised. The current meta-analysis aimed to assess the efficacy and safety of selected BMSC transplantation in patients with acute myocardial infarction (AMI) based on published randomized controlled trials (RCTs). METHODS: A systematic literature search of PubMed, Ovid LWW, BIOSIS Previews, and the Cochrane library from 1990 to 2014 was conducted. Results from RCTs involving subjects with AMI receiving selected BMSC therapy and followed up for at least 6 months were pooled. RESULTS: Eight trials with a total of 262 participants were included. Data were analyzed using a random effects model. Overall, selected BMSC therapy improved left ventricular ejection fraction (LVEF) by 3.17% (95% confidence interval [CI] 0.57-5.76, P=0.02), compared with the controls. There were trends toward reduced left ventricular end-systolic volume (LVESV) and fewer major adverse cardiac events (MACEs). Subgroup analysis revealed a significant difference in LVEF in favor of selected BMSC therapy with bone marrow mesenchymal stem cells (BMMSCs) as the cell type. CONCLUSIONS: Transplantation of selected BMSCs for patients with AMI is safe and induces a significant increase in LVEF with a limited impact on left ventricular remodeling.

Alterations in cardiac structure and function in a modified rat model of myocardial hypertrophy.

This study was aimed to establish a stable animal model of left ventricular hypertrophy (LVH) to provide theoretical and experimental basis for understanding the development of LVH. The abdominal aorta of male Wistar rats (80-100 g) was constricted to a diameter of 0.55 mm between the branches of the celiac and anterior mesenteric arteries. Echocardiography using a linear phased array probe was performed as well as pathological examination and plasma B-type natriuretic peptide (BNP) measurement at 3, 4 and 6 weeks after abdominal aortic constriction (AAC). The results showed that the acute mortality rate (within 24 h) of this modified rat model was 8%. Animals who underwent AAC demonstrated significantly increased interventricular septal (IVS), LV posterior wall (LVPWd), LV mass index (LVMI), cross-sectional area (CSA) of myocytes, and perivascular fibrosis; the ejection fraction (EF), fractional shortening (FS), and cardiac output (CO) were consistently lower at each time point after AAC. Notably, differences in these parameters between AAC group and sham group were significant by 3 weeks and reached peaks at 4th week. Following AAC, the plasma BNP was gradually elevated compared with the sham group at 3rd and 6th week. It was concluded that this modified AAC model can develop LVH, both stably and safely, by week four post-surgery; echocardiography is able to assess changes in chamber dimensions and systolic properties accurately in rats with LVH.

[Design of a satisfaction evaluation indicator system based on patients' experience of medical services].

OBJECTIVE: To construct a satisfaction evaluation indicator system based on patients' experiences of medical services. METHODS: A questionnaire was designed by expert interview and literature review and 400 copies were randomly handed out to inpatients and outpatients from five 3A-public hospitals in Shanghai. The patient's evaluation of importance of various factors in medical services was analyzed and the mean and weight of indicators in terms of recognition, importance and evaluation were determined to establish a satisfaction evaluation indicator system. RESULTS: A total of 396 valid questionnaires were retrieved, with an effective response rate of 99%. By analyzing survey data, the patient satisfaction evaluation indicator system was constructed with 5 primary indicators (hospital environment, medical procedures, attitude, and quality of care and patient rights) and 25 secondary indicators (convenient hospital environment, auxiliary facilities, reasonable arrangement, clearly mark, convenient appointment, simple procedures, short time, the attitude of medical staff, solutions of medical dispute, medical technology, treatment, medical equipment, medical expenses, respect, patient privacy, etc.). CONCLUSION: A patient satisfaction evaluation indicator system has been established based on patients' experience of medical services in the study, which may be applicable to measure patients' satisfaction and to improve medical services in hospitals.

miR-10a restores human mesenchymal stem cell differentiation by repressing KLF4.

miRNAs have recently been shown to play a significant role in human aging. However, data demonstrating the effects of aging-related miRNAs in human mesenchymal stem cells (hMSCs) are limited. We observed that hMSC differentiation decreased with aging. We also identified that miR-10a expression was significantly decreased with age by comparing the miRNA expression of hMSCs derived from young and aged individuals. Therefore, we hypothesized that the downregulation of miR-10a may be associated with the decreased differentiation capability of hMSCs from aged individuals. Lentiviral constructs were used to up- or downregulate miR-10a in young and old hMSCs. Upregulation of miR-10a resulted in increased differentiation to adipogenic, osteogenic, and chondrogenic lineages and in reduced cell senescence. Conversely, downregulation of miR-10a resulted in decreased cell differentiation and increased cell senescence. A chimeric luciferase reporter system was generated, tagged with the full-length 3'-UTR region of KLF4 harboring the seed-matched sequence with or without four nucleotide mutations. These constructs were cotransfected with the miR-10a mimic into cells. The luciferase activity was significantly repressed by the miR-10a mimic, proving the direct binding of miR-10a to the 3'-UTR of KLF4. Direct suppression of KLF4 in aged hMSCs increased cell differentiation and decreased cell senescence. In conclusion, miR-10a restores the differentiation capability of aged hMSCs through repression of KLF4. Aging-related miRNAs may have broad applications in the restoration of cell dysfunction caused by aging.

MicroRNA-26 was decreased in rat cardiac hypertrophy model and may be a promising therapeutic target.

MicroRNA (miR)-26 was found to be downregulated in cardiac diseases. In this study, the critical role of miR-26 in myocardial hypertrophy in both in vivo and in vitro was investigated. Sixteen male Wistar rats that underwent sham or transverse abdominal aortic constriction (TAAC) surgery were divided into control or TAAC group. Cardiomyocytes were isolated from neonatal Sprague-Dawley rats. Our study demonstrated that miR-26a/b was downregulated in both TAAC rat model and cardiomyocytes. The results of luciferase assays also suggested that glycogen synthase kinase 3ß (GSK3ß) may be a direct target of miR-26. The overexpression of miR-26 attenuated GSK3ß expression and inhibited myocardial hypertrophy. The downregulation of miR-26 reversed these effects. Furthermore, silence of GSK3ß gene phenocopied the anti-hypertrophy effects of miR-26, whereas overexpression of this protein attenuated the effects of miR-26. Taken together, these data suggest that miR-26 regulates pathological structural changes in the rat heart, which may be associated with suppression of the GSK3ß signaling pathway, and implicate the potential application of miR-26 in diagnosis and therapy of cardiac hypertrophy.

Metabolic profile of puerarin in rats after intragastric administration of puerarin solid lipid nanoparticles.

Puerarin has multiple pharmacological effects and is widely prescribed for patients with cardiovascular diseases including hypertension, cerebral ischemia, myocardial ischemia, diabetes mellitus, and arteriosclerosis. We have successfully prepared puerarin-loaded solid lipid nanoparticles (Pue-SLNs) for oral administration. Pue-SLNs are prepared using monostearin, soya lecithin, and poloxamer 188. SLNs may alter the course of puerarin absorption predominantly to and through lymphatic routes and regions, presumably following a transcellular path of lipid absorption, especially by enterocytes and polar epithelial cells of the intestine. The alteration of absorption might influence the metabolic profile of puerarin when incorporated into SLNs. In the present study, we investigated the metabolic profile of puerarin in rat plasma and urine using rapid resolution liquid chromatography-tandem mass spectrometry after a single-dose intragastric administration of Pue-SLNs in comparison with puerarin suspension. Two glucuronidated metabolites of puerarin, puerarin-4'-O-glucuronide and puerarin-7-O-glucuronide, were detected in rat plasma and urine after intragastric administration of Pue-SLNs, with the latter acting as the major metabolite. Similar results were found in rat plasma and urine after intragastric administration of puerarin suspension. The results suggest that incorporation of puerarin into SLNs does not change either the position of glucuronidation or the metabolic pathway of puerarin in rats.