Integrating Physiological Features and Proteomic Analyses Provides New Insights in Blue/Red Light-Treated Moso Bamboo (Phyllostachys edulis).

Bamboo is one of the most important nontimber forestry products in the world. Light is not only the most critical source of energy for plant photosynthesis but also involved in regulating the biological processes of plants. However, there are few reports on how blue/red light affects Moso bamboo. This study investigated the growth status and physiological responses of Moso bamboo (Phyllostachys edulis) to blue/red light treatments. The growth status of the bamboo plants was evaluated, revealing that both blue- and red-light treatments promoted plant height and overall growth. Gas exchange parameters, chlorophyll fluorescence, and enzyme activity were measured to assess the photosystem response of Moso bamboo to light treatments. Additionally, the blue light treatment led to a higher chlorophyll content and enzyme activities compared to the red light treatment. A tandem mass tag quantitative proteomics approach identified significant changes in protein abundance under different light conditions with specific response proteins associated with distinct pathways, such as photosynthesis and starch metabolism. Overall, this study provides valuable insights into the physiological and proteomic responses of Moso bamboo to blue/red light treatments, highlighting their potential impact on growth and development.

Prognostic role of tissue plasminogen activator in coronary artery disease with or without aortic valve sclerosis.

AIMS: We sought to investigate the relationship between circulating tissue plasminogen activator (t-PA) level and long-term outcomes in stable coronary artery disease patients with or without aortic valve sclerosis (AVSc). METHODS AND RESULTS: Serum levels of t-PA were determined in 347 consecutive stable angina patients with (n = 183) or without (n = 164) AVSc. Outcomes were prospectively recorded as planned clinic evaluations every 6 months up to 7 years. The primary endpoint was a composite of cardiovascular death and rehospitalization due to heart failure. The secondary endpoint included all-cause mortality, cardiovascular death, and rehospitalization due to heart failure. Serum t-PA was significantly higher in AVSc than in non-AVSc patients (2131.22 pg/mL vs. 1495.85 pg/mL, P < 0.001). For patients with AVSc, those with t-PA level above the median (>1840.68 pg/mL) were more likely to meet the primary and secondary endpoints (all P < 0.001). After adjusting for potential confounding factors, serum t-PA level remained significantly predictive for each endpoint in the Cox proportional hazard models. The prognostic value of t-PA was good, with an AUC-ROC of 0.753 (P < 0.001). The combination of t-PA with traditional risk factors improved the risk reclassification of AVSc patients, with a net reclassification index of 0.857 and an integrated discrimination improvement of 0.217 (all P < 0.001). However, for patients without AVSc, both primary and secondary endpoints were similar, irrespective of t-PA levels. CONCLUSIONS: Elevated circulating t-PA confers an increased risk for poor long-term clinical outcomes in stable coronary artery disease patients with AVSc.

Stathmin 1 is a biomarker for diagnosis of microvascular invasion to predict prognosis of early hepatocellular carcinoma.

Microvascular invasion (MVI) is presently evaluated as a high-risk factor to be directly relative to postoperative prognosis of hepatocellular carcinoma (HCC). Up to now, diagnosis of MVI mainly depends on the postoperative pathological analyses with H&E staining assay, based on numbers and distribution characteristics of MVI to classify the risk levels of MVI. However, such pathological analyses lack the specificity to discriminate MVI in HCC specimens, especially in complicated pathological tissues. In addition, the efficiency to precisely define stages of MVI is not satisfied. Thus, any biomarker for both conforming diagnosis of MVI and staging its levels will efficiently and effectively promote the prediction of early postoperative recurrence and metastasis for HCC. Through bioinformatics analysis and clinical sample verification, we discovered that Stathmin 1 (STMN1) gene was significantly up-regulated at the locations of MVI. Combining STMN1 immunostaining with classic H&E staining assays, we established a new protocol for MVI pathological diagnosis. Next, we found that the degrees of MVI risk could be graded according to expression levels of STMN1 for prognosis prediction on recurrence rates and overall survival in early HCC patients. STMN1 affected epithelial-mesenchymal transformation (EMT) of HCC cells by regulating the dynamic balance of microtubules through signaling of "STMN1-Microtubule-EMT" axis. Inhibition of STMN1 expression in HCC cells reduced their lung metastatic ability in recipients of mouse model, suggesting that STMN1 also could be a potential therapeutic target for inhibiting HCC metastasis. Therefore, we conclude that STMN1 has potentials for clinical applications as a biomarker for both pathological diagnosis and prognostic prediction, as well as a therapeutic target for HCC.

A Three-Dimensional Imaging Method for the Quantification and Localization of Dynamic Cell Tracking Posttransplantation.

Cell transplantation has been proposed as a promising therapeutic strategy for curing the diseases requiring tissue repairing and functional restoration. A preclinical method to systematically evaluate the fates of donor cells in recipients, spatially and temporally, is demanded for judging therapeutic potentials for the particularly designed cell transplantation. Yet, the dynamic cell tracking methodology for tracing transplanted cells in vivo is still at its early phase. Here, we created a practical protocol for dynamically tracking cell via a three-dimensional (3D) technique which enabled us to localize, quantify, and overall evaluate the transplanted hepatocytes within a liver failure mouse model. First, the capacity of 3D bioluminescence imaging for quantifying transplanted hepatocytes was defined. Images obtained from the 3D bioluminescence imaging module were then combined with the CT scanner to reconstruct structure images of host mice. With those reconstructed images, precise locations of transplanted hepatocytes in the liver of the recipient were dynamically monitored. Immunohistochemistry staining of transplanted cells, and the serology assay of liver panel of the host mice were applied to verify the successful engraftment of donor cells in the host livers. Our protocol was practical for evaluating the engraftment efficiency of donor cells at their preclinical phases, which is also applicable as a referable standard for studying the fates of other transplanted cells, such as stem cell-derived cell types, during preclinical studies with cell transplantation therapy.

Release Profile of Cardiac Troponin T and Risk Factors of Postoperative Myocardial Injury in Patients Undergoing CABG.

BACKGROUND: Cardiac troponin T (cTnT) is currently one of the important indicators for clinical diagnosis of myocardial injury, which is inevitable in cardiac surgery, especially coronary artery bypass grafting (CABG). Describing the release profile of cTnT and finding out the risk factors of postoperative myocardial injury (PMI) are of great significance. The purposes of this study are to explore the release profile of cTnT in patients undergoing CABG and to search for independent risk factors of PMI. METHODS: In this retrospective study, clinical data of CABG patients were collected. The cTnT was measured at 24 hours before and 6, 12, 24, 48, 72, 96 and 120 hours after operation separately. The release profiles and peak time of cTnT in total cohort and sub-cohorts were observed. Independent risk factors of PMI were explored via univariate and multivariate logistic regression analyses. RESULTS: In total, 2084 patients were enrolled, including 998 patients in a cTnT group and 1086 patients in a high-sensitive cTnT (hs-cTnT) group. PMI was recognized in 797 patients. In both groups, cTnT showed a trend of rising first and then falling within 120 hours after operation. The peak cTnT appeared within 12-24 hours after operation, while the peak hs-cTnT occurred mostly within 24-48 hours after operation. Univariate logistic analysis showed that body mass index (BMI), New York Heart Association (NYHA) classification, coronary artery disease (CAD) classification, cerebrovascular disease, left ventricular ejection fraction, number of diseased vessels, valvular disease, intra-aortic balloon pump (IABP) implantation, chronic obstructive pulmonary disease, pulmonary hypertension, previous percutaneous coronary intervention (PCI), BMI, bypass graft number, cardiopulmonary bypass, and preoperative cTnT were related risk factors. Multivariate logistic regression analysis showed that NYHA classification, CAD classification, valvular disease, IABP implantation, pulmonary hypertension, previous PCI, bypass graft number, cardiopulmonary bypass, and preoperative cTnT were independent risk factors of PMI. CONCLUSION: NYHA classification, CAD classification, valvular disease, IABP implantation, pulmonary hypertension, previous PCI, bypass graft number, cardiopulmonary bypass, and preoperative cTnT are independent risk factors of PMI in patients undergoing CABG.

miR-301a-PTEN-AKT Signaling Induces Cardiomyocyte Proliferation and Promotes Cardiac Repair Post-MI.

Adult hearts are hard to recover after cardiac injury due to the limited proliferative ability of cardiomyocytes. Emerging evidence indicates the induction of cell cycle reentry of cardiomyocytes by special treatment or stimulation, which offers adult heart regenerative potential. Herein, a microRNA (miRNA) screening in cardiomyocytes identified miR-301a enriched specially in the neonatal cardiomyocytes from rats and mice. Overexpression of miR-301a in primary neonatal cardiomyocytes and H9C2 cells induced G1/S transition of the cell cycle, promoted cellular proliferation, and protected cardiomyocytes against hypoxia-induced apoptosis. Adeno-associated virus (AAV)9-mediated cardiac delivery of miR-301a to the mice model with myocardial infarction (MI) dramatically promoted cardiac repair post-MI in vivo. Phosphatase and tensin homolog (PTEN)/phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway was confirmed to mediate miR-301a-induced cell proliferation in cardiomyocytes. Loss of function of PTEN mimicked the miR-301a-induced phenotype, while gain of function of PTEN attenuated the miR-301a-induced cell proliferation in cardiomyocytes. Application of RG7440, a small molecule inhibitor of AKT, blocked the function of miR-301a in cardiomyocytes. The current study revealed a miRNA signaling in inducing the cell cycle reentry of cardiomyocytes in the injured heart, and it demonstrated the miR-301a/PTEN/AKT signaling as a potential therapeutic target to reconstitute lost cardiomyocytes in mammals.

Daily Branched-Chain Amino Acid Intake and Risks of Obesity and Insulin Resistance in Children: A Cross-Sectional Study.

OBJECTIVE: This study aimed to investigate the association of daily branched-chain amino acid (BCAA) intake with the risks of obesity and insulin resistance in children of mothers with gestational diabetes mellitus (GDM). METHODS: Daily BCAA intake was calculated by using a validated food frequency questionnaire in 996 children of mothers with GDM. The odds ratios (ORs) (95% CI) of childhood obesity and insulin resistance were obtained using logistic regression models. RESULTS: The multivariable-adjusted ORs for overweight and insulin resistance increased across quartiles of daily BCAA intake (P < 0.05 for trend). Multivariable-adjusted ORs for each 1-SD increase in BCAA intake were 1.37 (1.16-1.62) for overweight and 1.19 (1.02-1.38) for insulin resistance. After additional adjustment of children's daily total energy intake, the OR was still significant for overweight risk but no longer significant for insulin resistance. There were positive associations of daily leucine, isoleucine, and valine intake with the risks for overweight and insulin resistance. CONCLUSIONS: Daily BCAA intake was associated with increased risks for overweight and insulin resistance in children of mothers with GDM, but this association was not fully independent of children's daily energy intake. Restriction in dietary BCAA may help prevent childhood obesity and insulin resistance.

Glucose metabolism among obese and non-obese children of mothers with gestational diabetes.

OBJECTIVES: Abdominal obesity is more closely associated with diabetes than general obesity in adults, however, it is unknown which kind of obesity is more closely associated with abnormal glucose metabolism in children. RESEARCH DESIGN AND METHODS: We recruited 973 children (aged 3.08±1.06) of mothers with prior gestational diabetes mellitus (GDM). Children's height, weight, waist circumstance, fasting glucose and insulin were measured using standardized methods. Logistic regression models were used to assess the single and joint associations of general and abdominal obesity with the risks of hyperglycemia (the upper quartile of fasting glucose), insulin resistance (the upper quartile of homeostatic model assessment of insulin resistance (HOMA-IR)), and ß-cell dysfunction (the lower quartile of HOMA-%ß). RESULTS: Compared with normal weight children, children with general overweight/obesity had higher levels of HOMA-IR and HOMA-%ß, higher ORs for hyperglycemia (1.56, 95% CI 1.06 to 2.30) and insulin resistance (3.44, 95% CI 2.32 to 5.09), but a lower OR for ß-cell dysfunction (0.65, 95% CI 0.41 to 1.04). Children with abdominal obesity had an increased risk of insulin resistance (2.54, 95% CI 1.71 to 3.76) but not hyperglycemia and ß-cell dysfunction compared with children with normal waist circumstance. In the joint analyses, general overweight children with and without abdominal obesity had an increased risk of hyperglycemia and insulin resistance compared with normal weight children. CONCLUSIONS: General obesity was more closely associated with abnormal glucose metabolism than abdominal obesity in children of mothers with GDM.

MiR-301a promotes embryonic stem cell differentiation to cardiomyocytes.

BACKGROUND: Cardiovascular disease is the leading cause of death worldwide. Tissue repair after pathological injury in the heart remains a major challenge due to the limited regenerative ability of cardiomyocytes in adults. Stem cell-derived cardiomyocytes provide a promising source for the cell transplantation-based treatment of injured hearts. AIM: To explore the function and mechanisms of miR-301a in regulating cardiomyocyte differentiation of mouse embryonic stem (mES) cells, and provide experimental evidence for applying miR-301a to the cardiomyocyte differentiation induction from stem cells. METHODS: mES cells with or without overexpression of miR-301a were applied for all functional assays. The hanging drop technique was applied to form embryoid bodies from mES cells. Cardiac markers including GATA-4, TBX5, MEF2C, and α-actinin were used to determine cardiomyocyte differentiation from mES cells. RESULTS: High expression of miR-301a was detected in the heart from late embryonic to neonatal mice. Overexpression of miR-301a in mES cells significantly induced the expression of cardiac transcription factors, thereby promoting cardiomyocyte differentiation and beating cardiomyocyte clone formation. PTEN is a target gene of miR-301a in cardiomyocytes. PTEN-regulated PI3K-AKT-mTOR-Stat3 signaling showed involvement in regulating miR-301a-promoted cardiomyocyte differentiation from mES cells. CONCLUSION: MiR-301a is capable of promoting embryonic stem cell differentiation to cardiomyocytes.

Joint Associations of Maternal Gestational Diabetes and Hypertensive Disorders of Pregnancy With Overweight in Offspring.

Objectives: Either maternal gestational diabetes mellitus (GDM) or hypertensive disorder of pregnancy (HDP) is associated with an increased risk of obesity in the offspring. However, their joint associations with obesity in offspring remain unclear. We investigated the joint associations of maternal GDM and HDP with childhood overweight in offspring. Methods: We performed a large study in 1967 mother-child pairs. Maternal GDM was diagnosed according to the 1999 World Health Organization (WHO) criteria. HDP was defined as self-reported doctor-diagnosed hypertension or treatment of hypertension (including gestational hypertension, preeclampsia, sever preeclampsia or eclampsia) after 20 weeks of gestation on the questionnaire. Body mass index (BMI) for age Z-score and childhood overweight were evaluated according to WHO growth reference. We used the general linear models to compare children's Z score for BMI and logistic regression models to estimate odds ratios of childhood overweight according to maternal different status of GDM and HDP. Results: Offspring of mothers with both GDM and HDP had a higher BMI for age Z-score (0.63 vs. 0.03, P < 0.001) than children born to normotensive and normoglycemic pregnancy. After adjustment for maternal and children's major confounding factors, joint GDM and HDP were associated with increased odds ratios of offspring's overweight compared with normotensive and normoglycemic pregnancy (2.97, 95% confidence intervals [CIs] 1.65-5.34) and GDM alone (2.06, 95% CIs 1.20-3.54), respectively. After additional adjustment for maternal pre-pregnancy BMI and gestational weight gain, joint maternal GDM, and HDP was still associated with an increased risk of offspring's overweight compared with the maternal normotensive, and normoglycemic group but became to have a borderline increased risk compared with the maternal GDM alone group. Conclusions: Maternal GDM alone or joint GDM and HDP were associated with increased ratios of offspring's overweight.

Association Between Serum Leptin Level and Calcific Aortic Valve Disease.

Background The pathophysiological process of calcific aortic valve disease (CAVD) is similar to that of atherosclerosis. Leptin accelerates the process of atherosclerosis. We sought to examine the relationship between leptin and CAVD. Methods and Results Serum leptin was measured in 397 consecutive patients undergoing standard transthoracic echocardiography and Doppler flow imaging. Multiple logistic regression analyses were used to assess the association between leptin and CAVD. Western blotting was performed to detect the expression of phosphorylated and total extracellular signal-regulated kinase. Serum leptin (median) was higher in 200 patients with CAVD than that in 197 non-CAVD controls (20.07 versus 9.03 ng/mL; P<0.01). Leptin correlated positively with age (r=0.37, P<0.01) and negatively with estimated glomerular filtration rate (r=-0.37, P<0.01). Multivariate analysis indicated that elevated leptin was an independent determinant for the presence of CAVD (P<0.01). Receiver-operating characteristic curve analysis of leptin to detect the presence of CAVD showed that the area under the curve was 0.74 (95% CI, 0.69-0.79; P<0.01). The diagnostic value of leptin for the detection of CAVD was higher among younger patients (aged ≤65 years) or those with at least mildly reduced renal function (estimated glomerular filtration rate ≤82.06 mL/min per 1.73 m2). The activation of extracellular signal-regulated kinase 1/2 was stronger in calcific aortic valves than in normal aortic valves. Conclusions Elevated leptin is associated with the presence of CAVD, especially among younger patients or those with renal dysfunction.

Fasudil preserves lung endothelial function and reduces pulmonary vascular remodeling in a rat model of end­stage pulmonary hypertension with left heart disease.

Pulmonary hypertension (PH) due to left heart disease (LHD) is a common condition associated with significant morbidity. It contributes to the elevation of pulmonary vascular resistance and mean pulmonary pressure, eventually leading to heart failure and even mortality. The present study aimed to explore the potential efficacy of late and long­term treatment with a Rho­kinase (ROCK) signaling inhibitor, namely fasudil, in a rat model of end­stage PH­LHD. The PH­LHD model was established by supracoronary aortic banding, and the effect of fasudil treatment on the progression of PH­LHD was monitored. After 9 weeks (63 days) of supracoronary aortic banding, a significant increase in mean pulmonary pressure and RV systolic pressure was observed in the rats, associated with increased RhoA/ROCK activity in the lungs. Therapy with fasudil (30 mg/kg/day, intraperitoneal) for 4 weeks from postoperative day 35 reversed the hemodynamic disorder and prevented pulmonary vascular remodeling in rats with PH­LHD. In addition, the blockade of ROCK signaling by fasudil decreased the protein levels of endothelin­1 (ET­1) and the mRNA expression levels of endothelin A receptor and promoted the production of nitric oxide (NO) in rats with PH­LHD. Furthermore, fasudil inhibited the migration of human pulmonary microvascular endothelial cells and the proliferation of pulmonary artery smooth muscle cells induced by ET­1. Therefore, this late, long­term blockade of the ROCK pathway by fasudil may be a promising strategy to reverse hemodynamic dysfunction and impede the development of end­stage PH­LHD in patients.

Serum Magnesium Concentration Is Inversely Associated with Albuminuria and Retinopathy among Patients with Diabetes.

Aim. To investigate the association between serum magnesium levels and microvascular complications among patients with diabetes. Methods. Patients with diabetes were recruited between April 2012 and January 2015. All patients received an assay of serum magnesium concentration, were screened for 24 h albumin excretion rate, and underwent nonmydriatic fundus photography. Albuminuria and retinopathy were defined accordingly. A total of 3,100 patients with normal serum magnesium levels were included in this study. Results. Patients with albuminuria and/or retinopathy had lower levels of serum magnesium than patients without these complications (P < 0.001). The prevalence of isolated albuminuria, isolated retinopathy, and combined albuminuria and retinopathy decreased as the concentration of serum magnesium increased. Multiple logistic regression analysis indicated that the odds ratio for isolated albuminuria, isolated retinopathy, and concomitant albuminuria and retinopathy decreased by approximately 20% for every 0.1 mmol/L increase in serum magnesium concentration. Conclusion. Serum magnesium levels were negatively associated with the risk of diabetic microvascular complications among patients with serum magnesium levels within the normal range.