Development of a nutritional risk screening tool for preterm children in outpatient settings during a complementary feeding period: a pilot study.

BACKGROUND: A complementary feeding (CF) period is necessary for nutritional and developmental reasons. Preterm children encounter more feeding problems than their term counterparts in the CF period. The goal of this study was to develop a nutritional risk screening tool specific to preterm children (the NRSP) in outpatient settings in the CF period, with the expectation of providing a standardised process to determine feeding problems and subsequently offering targeted nutritional advice. METHODS: This study was a 2-phase study consisting of the development and evaluation phases. In the development phase, the items of the NRSP were initially developed based on references and the Delphi expert consultation method. Second, 329 preterm individuals with corrected ages from 5 to 36 months were enrolled. The participating preterm children were interviewed with the NRSP and anthropometric measurements, and underwent intellectual developmental tests and biochemistry detection (haemoglobin, red blood cell count, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, serum iron, vitamin D). Third, preterm children's anthropometric parameters were remeasured 1 month (for infants whose corrected age was 5-11 months) or 3 months (for children whose corrected age was 12-36 months) after the interview. Data in the development phase were analysed via univariate and binary logistic regression analysis sequentially to assign scores for items of the NRSP and to generate the models to predict underweight, stunting, and microcephaly of the NRSP. In the evaluation phase, another 605 preterm individuals were recruited to undergo the interview, anthropometric measurements, intellectual developmental tests, and biochemistry detection as in the development phase. Interrater reliability, test-retest reliability, area under the curve (AUC), accuracy, sensitivity, specificity, the positive/negative predictive value (P/NPV), the positive/negative likelihood ratio (LR+/-), and the correlation coefficient by Spearman's correlation analysis (rs) were used to assess the reliability and validity of the NRSP. Finally, anthropometric parameters, biochemistry levels, and intellectual development quotients (DQs) from the development and evaluation phases between the high- and low-risk groups classified by the NRSP were compared using a t-test. RESULTS: The κ coefficients of the interrater and test-retest reliability of the NRSP were all above 0.600, which meant that the reliability of the NRSP was moderate to substantial. The NRSP exhibited relatively higher efficiency in predicting underweight and stunting, with AUCs, accuracies, specificities, and NPVs near to or greater than 0.900, sensitivities above 0.600, PPVs above 0.400, LR + s near to or greater than 10, and rss above 0.400. On the other hand, the NRSP manifested a weaker ability in predicting microcephaly, with most of the values of validity indicators lower than those of underweight and stunting prediction. Z scores of body weight, body length and head circumference, as well as DQs, were all higher in the low-risk groups than in the high-risk groups. There were no significant differences with respect to biochemistry levels between the high- and low-risk groups. CONCLUSION: The NRSP shows moderate to substantial reliability and validity in predicting underweight, stunting, and microcephaly. Health care staff should shed light on improving the feeding practices of preterm children with high nutritional risk classified by the NRSP to facilitate their physical growth and intellectual development. More research is expected to promote the NRSP models.

Research Progress on the Positive and Negative Regulatory Effects of Rhein on the Kidney: A Review of Its Molecular Targets.

Currently, both acute kidney injury (AKI) and chronic kidney disease (CKD) are considered to be the leading public health problems with gradually increasing incidence rates around the world. Rhein is a monomeric component of anthraquinone isolated from rhubarb, a traditional Chinese medicine. It has anti-inflammation, anti-oxidation, anti-apoptosis, anti-bacterial and other pharmacological activities, as well as a renal protective effects. Rhein exerts its nephroprotective effects mainly through decreasing hypoglycemic and hypolipidemic, playing anti-inflammatory, antioxidant and anti-fibrotic effects and regulating drug-transporters. However, the latest studies show that rhein also has potential kidney toxicity in case of large dosages and long use times. The present review highlights rhein's molecular targets and its different effects on the kidney based on the available literature and clarifies that rhein regulates the function of the kidney in a positive and negative way. It will be helpful to conduct further studies on how to make full use of rhein in the kidney and to avoid kidney damage so as to make it an effective kidney protection drug.

Protective effect of Rhein against vancomycin-induced nephrotoxicity through regulating renal transporters and Nrf2 pathway.

Vancomycin (VCM)'s nephrotoxicity limits its application and therapeutic efficiency. The aim of this study was to determine the protective effect of rhein against VCM-induced nephrotoxicity (VIN). VIN models were established in rats and NRK-52E cells. Rhein up-regulated the expressions of renal organic anion transporter (Oat) 1, Oat3, organic cation transporter 2 (Oct2), multidrug resistance-associated protein 2 (Mrp2), mammal multidrug and toxin extrusion proteins 1 (Mate 1) and P-glycoprotein (P-gp) to facilitate the efflux of plasma creatinine, blood urea nitrogen (BUN), and plasma indoxyl sulfate. Rhein increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) to regulate the expression of Mrp2, P-gp, and Mate 1. The increased level of superoxide dismutase (SOD), decreased level of malondialdehyde (MDA) and reduced number of apoptosis cells were observed after treatment of rhein. Rhein decreased the number of apoptosis cells as well as increased the expression of B-cell lymphoma-2 (Bcl-2) and decreased expressions of Bcl-2-like protein 4 (Bax). ML385, as a typical inhibitor of Nrf2, reversed the protective effects of rhein in cells. Rhein oriented itself in the site of Keap1, inhibiting the Keap1-Nrf2 interaction. Rhein ameliorated VIN mainly through regulating the expressions of renal transporters and acting on Nrf2 pathway.

Iron Supplementation Is Associated with Improvement of Motor Development, Hemoglobin Level, and Weight in Preterm Infants during the First Year of Life in China.

Iron supplementation is recommended for preterm infants due to impaired iron endowment. However, the health outcomes of this recommendation remain controversial. Thus, this study aimed to determine the association of iron supplementation with neurobehavioral development, hemoglobin (Hb), and anthropometric characteristics in preterm infants. A retrospective cohort design was applied to collect data from 1568 preterm infants at 0-3 months of corrected age (mo CA) from a hospital in South China. Infants were categorized into a 3-month iron supplementation group (IG, n = 697) or a control group (CG, n = 871) according to medical records, and then followed through to 12 mo CA. Data on neurobehavioral development, anthropometry, Hb level, history of diseases, and nutrition were collected at 3, 6, and 12 mo CA. The results showed that, compared with the CG, iron supplementation was positively related to improved gross motor skills and weight at 6 mo CA (ß = 1.894, ß = 5.322) and 12 mo CA (ß = 4.019, ß = 6.830) and fine motor skills at 12 mo CA (ß = 1.980), after adjustment for confounding factors including illness, nutritional supplements, and diet. Iron supplementation was also related to elevated Hb levels and its increase at 3 mo CA (ß = 2.196, ß = 3.920) and 6 mo CA (ß = 3.011, ß = 7.259). In conclusion, iron supplementation for 3 months in Chinese preterm infants is positively associated with improved motor development, elevated Hb levels, and higher body weight during the first year of life.

Targeting renal OATs to develop renal protective agent from traditional Chinese medicines: Protective effect of Apigenin against Imipenem-induced nephrotoxicity.

Imipenem (Imp) is a widely used broad-spectrum antibiotic. However, renal adverse effects limit its clinical application. We previously reported that organic anion transporters (OATs) facilitated the renal transport of Imp and contributed its nephrotoxicity. Natural flavonoids exhibited renal protective effect. Here, we aimed to develop potent OAT inhibitors from traditional Chinese medicines (TCMs) and to evaluate its protective effect against Imp-induced nephrotoxicity. Among 50 TCMs, Tribuli Fructus, Platycladi Cacumen, and Lycopi Herba exhibited potent inhibition on OAT1/3. After screening their main components, Apigenin strongly inhibited Imp uptake by OAT1/3-HEK293 cells with IC50 values of 1.98 ± 0.36 µM (OAT1) and 2.29 ± 0.88 µM (OAT3). Moreover, Imp exhibited OAT1/3-dependent cytotoxicity, which was alleviated by Apigenin. Furthermore, Apigenin ameliorated Imp-induced nephrotoxicity in rabbits, and reduced the renal secretion of Imp. Apigenin inhibited intracellular accumulation of Imp and sequentially decreased the nephrocyte toxicity in rabbit primary proximal tubule cells (rPTCs). Apigenin, a flavone widely distributed in TCMs, was a potent OAT1/3 inhibitor. Through OAT inhibition, at least in part, Apigenin decreased the renal exposure of Imp and consequently protected against the nephrotoxicity of Imp. Apigenin can be used as a promising agent to reduce the renal adverse reaction of Imp in clinic.

Plant food anthocyanins inhibit platelet granule secretion in hypercholesterolaemia: Involving the signalling pathway of PI3K-Akt.

Controlling platelet granule secretion has been considered an effective strategy to dampen thrombosis and prevent atherosclerosis. Anthocyanins are natural plant pigments and possess a wide range of biological activities, including cardiovascular protective activity. In the present study we explored the effects and the potential mechanisms of anthocyanins on platelet granule secretion in hypercholesterolemia. In a randomised, double-blind clinical trial, 150 hypercholesterolaemic individuals were treated with purified anthocyanins (320 mg/day) or placebo for 24 weeks. Anthocyanins consumption significantly reduced plasma levels of ß-thromboglobulin (ß-TG), soluble P-selectin, and of Regulated on Activation Normal T cell Expressed and Secreted (RANTES) as compared with the placebo. A minor reduction in platelet factor 4 (PF4) and transforming growth factor ß1 (TGF-ß1) levels were also observed. In in vitro experiments, we observed that puriÓ¿ed anthocyanin mixture, as well as its two main anthocyanin components, delphinidin-3-glucoside (Dp-3-g) and cyanidin-3-glucoside (Cy-3g) directly inhibited platelet á-granule, dense granule, and lysosome secretion evaluated by P-selectin, RANTES, ß-TG, PF4, TGF-ß1, serotonin, ATP, and CD63 release. Further, anthocyanins inhibited platelet PI3K/Akt activation and consequently attenuated eNOS phosphorylation and cGMP production, thus interrupting MAPK activation. LY294002, a PI3K inhibitor, did not cause additional inhibitory efficacy, indicating that anthocyanin-induced effects may be involved in inhibition of the PI3K/Akt signalling pathway. These results provide evidence that by inhibiting platelet granule secretion, anthocyanins may be a potent cardioprotective agent.

Anthocyanin supplementation improves HDL-associated paraoxonase 1 activity and enhances cholesterol efflux capacity in subjects with hypercholesterolemia.

CONTEXT AND OBJECTIVE: Paraoxonase 1 (PON1), an enzyme associated with high-density lipoprotein (HDL-PON1), is reported to have antioxidant and cardioprotective properties. The aim of the present study was to investigate the effects of anthocyanins on the HDL-PON1 activity and cholesterol efflux capacity in hypercholesterolemic subjects. DESIGN AND PARTICIPANTS: A total of 122 hypercholesterolemic subjects were given 160 mg of anthocyanins twice daily or placebo (n = 61 of each group) for 24 weeks in a double-blind, randomized, placebo-controlled trial. Participants and investigators were masked to treatment allocation. RESULTS: Anthocyanin consumption significantly increased HDL cholesterol and decreased low -density lipoprotein cholesterol concentrations compared with placebo (P < .018 and P < .001, respectively). Anthocyanin supplementation also increased the activity of HDL-PON1 compared with placebo (P < .001). Furthermore, cholesterol efflux capacity was increased more in the anthocyanin group (20.0% increase) than in the placebo group (0.2% increase) (P < .001). The negative correlations established between HDL-PON1 activity and the levels of lipid hydroperoxides associated with HDL confirm the relationship between PON1 activity and lipid peroxidation of lipoproteins. Furthermore, a strong positive correlation was noted between increased HDL-PON1 activity and improved cholesterol efflux capacity both before and after adjustment for HDL cholesterol and apolipoprotein AI in anthocyanin-treated subjects (both P < .001). Inhibition of HDL-PON1 activity strongly prevented the antioxidant ability of HDL and attenuated the cholesterol efflux capacity of subjects from anthocyanin group. CONCLUSIONS: Our observations suggest that the alterations of PON1 activity by anthocyanin observed in hypercholesterolemic HDL reflect a shift to an improvement of cholesterol efflux capacity of HDL and may provide a link between anthocyanin and cardioprotective effects.

Optimization of microwave-assisted extraction of anthocyanins from mulberry and identification of anthocyanins in extract using HPLC-ESI-MS.

Anthocyanins are naturally occurring compounds that impart color to fruits, vegetables, and plants. This study aims to optimize the microwave-assisted extraction (MAE) conditions of anthocyanins from mulberry (M. atropurpurea Roxb.) using response surface methodology (RSM). A Box-Behnken experiment was employed in this regard. Methanol concentration, microwave power, and extraction time were chosen as independent variables. The optimized conditions of MAE were as follows: 59.6% acidified methanol, 425 W power, 25 (v/w) liquid-to-solid ratio, and 132 s time. Under these conditions, 54.72 mg anthocyanins were obtained from 1.0 g mulberry powder. Furthermore, 8 anthocyanins were identified by high-performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS) in mulberry extract. The results showed that cyanidin-3-glucoside and cyanidin-3-rutinoside are the major anthocyanins in mulberry. In addition, in comparison with conventional extraction, MAE is more rapid and efficient for extracting anthocyanins from mulberry.

Purified anthocyanin supplementation improves endothelial function via NO-cGMP activation in hypercholesterolemic individuals.

BACKGROUND: Anthocyanins have been shown to improve endothelial function in animal models. However, whether these compounds have similar beneficial effects in humans is largely unknown. METHODS: In a short-term crossover study, 12 hypercholesterolemic individuals were given oral anthocyanins (320 mg) isolated from berries or placebo. Brachial artery flow-mediated dilation (FMD) was assessed before and after the intervention. In a long-term intervention trial (12 weeks), 150 hypercholesterolemic individuals were given anthocyanins (320 mg/day, n = 75) or placebo (n = 75), after which we measured FMD, plasma cGMP, and other serum biomarkers. Another short-term intervention was conducted in the presence of NO-cGMP inhibitors in 6 people and in a rat aortic ring model (n = 8). RESULTS: Significant increases of FMD from 8.3% (0.6%) at baseline to 11.0% (0.8%) at 1 h and 10.1% (0.9%) at 2 h were observed after short-term anthocyanin consumption, concomitantly with increases of plasma anthocyanin concentrations (P < 0.05). In the study participants who received long-term anthocyanin intervention, compared with the control group, we observed significant increases in the FMD (28.4% vs 2.2%), cGMP (12.6% vs -1.2%), and HDL-cholesterol concentrations, but decreases in the serum soluble vascular adhesion molecule-1 and LDL cholesterol concentrations (P < 0.05). The changes in the cGMP and HDL cholesterol concentrations positively correlated with FMD in the anthocyanin group (P < 0.05). In the presence of NO-cGMP inhibitors, the effects of anthocyanin on endothelial function were abolished in human participants and in a rat aortic ring model. CONCLUSIONS: Anthocyanin supplementation improves endothelium-dependent vasodilation in hypercholesterolemic individuals. This effect involves activation of the NO-cGMP signaling pathway, improvements in the serum lipid profile, and decreased inflammation.

Anthocyanin extract from black rice significantly ameliorates platelet hyperactivity and hypertriglyceridemia in dyslipidemic rats induced by high fat diets.

Our previous studies have demonstrated that anthocyanin extract from black rice (AEBR) inhibits atherosclerosis. Whether dietary AEBR supplementation can affect platelet function, an important factor in the pathogenesis of cardiovascular diseases, remains unclear. The aim of the present study is to explore the effects and mechanisms of dietary AEBR supplementation on platelet function and lipid profile in dyslipidemic rats. We demonstrated herein that thromboxane A(2), the thrombogenic ratio of thromboxane A2 and prostacyclin, serum calmodulin, and soluble P-selectin were significantly decreased in rats fed a high fat diet supplemented with AEBR. AEBR supplementation also remarkably lowered serum triglyceride and raised hepatic CPT-1 mRNA expression. These findings suggest that dietary intake of AEBR reduces platelet hyperactivity, hypertriglyceridemia, and body weight gain, and facilitates in the maintenance of optimal platelet function in dyslipidemic rats induced by high fat diets.

Cyanidin-3-O-ß-glucoside improves obesity and triglyceride metabolism in KK-Ay mice by regulating lipoprotein lipase activity.

BACKGROUND: Cyanidin-3-O-ß-glucoside (Cy-3-g)-rich foods have been reported to inhibit the onset of obesity, but whether the pure anthocyanin supplementation affects obesity remains uncertain. RESULTS: Cy-3-g supplementation significantly reduced obesity, accumulation of fat in visceral adipose and liver tissues, and plasma triglyceride levels. Furthermore, adenosine monophosphate (AMP)-activated protein kinase phosphorylation (pAMPK) in the skeletal muscle and visceral adipose were significantly increased by Cy-3-g consumption. This was followed by the activation of lipoprotein lipase (LPL) in plasma and skeletal muscle but the suppression of this enzyme in visceral adipose. LPL activation in skeletal muscle cells and its suppression in adipocytes by Cy-3-g were blocked by inhibition of pAMPK. CONCLUSION: Our present data thus demonstrate that Cy-3-g improves obesity and triglyceride metabolism in KK-Ay mice. The underlying mechanism is found to be partly related to the activation of LPL in plasma and skeletal muscle, and inhibition of LPL in adipose tissue following the activation of pAMPK.