Plasma Level of Apelin as a Promising Factor for Retinopathy of Prematurity.

INTRODUCTION: To investigate the relevance of plasma levels of apelin and other risk factors in infants with retinopathy of prematurity (ROP). METHODS: This was a single-center cross-sectional study. Fifty preterm infants with ROP and 50 preterm infants without ROP were enrolled. The analysis included evaluation of gestational age, birth weight, and measurement of plasma concentrations of apelin, vascular endothelial growth factor (VEGF), erythropoietin (EPO), and insulin-like growth factor (IGF-1) using enzyme-linked immunosorbent assay. RESULTS: The mean BW and GA of babies with ROP were considerably lower than those without ROP (P < 0.001, P = 0.003, respectively). Plasma levels of VEGF, EPO, and IGF-1 were all lower in babies with ROP (all P < 0.001), while plasma apelin levels were greater (P < 0.001). We compared the sensitivity and selected the best cut-offs while keeping the specificity constant (80.0%). Among all the criteria, plasma apelin levels had the best sensitivity (72%), with a 21.08 pg/mL cut-off. Multivariable logistic regression analyses showed that the plasma level of apelin was the only parameter associated with ROP (P = 0.02, OR = 16, CI = 95%: 1.54-166.53). The AUC of the multivariable regression model that comprised GA, BW alone was 0.67, while the model that included apelin was 0.90. CONCLUSIONS: Plasma apelin level demonstrated good sensitivity and specificity with regard to the association of ROP, the inclusion of apelin may be a promising factor to include in screening criteria.

Design of pH-sensitive peptides from natural antimicrobial peptides for enhancing polyethylenimine-mediated gene transfection.

BACKGROUND: Poor endosomal release is a major barrier of polyplex-mediated gene transfection. Antimicrobial peptides (AMPs) are commonly used to improve polyethylenimine (PEI)-mediated gene transfection by increasing endosomal release. In the present study, we designed novel pH-sensitive peptides that highly enhance transfection efficiency compared to their parent peptides. METHODS: Two analogues of melittin (Mel) and RV-23 (RV) were synthesized by replacing the positively-charged residues in their sequences with glutamic acid residues. The pH-sensitive lysis ability of the peptides, the effect of the peptides on physicochemical characteristics, the intracellular trafficking, the transfection efficiency, and the cytotoxicity of the polyplexes were determined. RESULTS: The acidic peptides showed pH-sensitive lytic activity. The hemolytic activity of acidic peptides at pH 5.0 was higher than that at pH 7.4. The incorporation of acidic peptides did not affect the DNA binding ability of PEI but affected the physicochemical characteristics of the PEI/DNA polyplexes, which may be beneficial for endosomal release and gene transfection. The incorporation of acidic peptides into PEI/DNA polyplexes enhanced the PEI-mediated transfection efficiency corresponding to up to 42-fold higher luciferase activity compared to that of PEI alone. CONCLUSIONS: The results of the present study indicate that replacement of positively-charged residues with glutamic acid residues in the AMP sequence yields pH-sensitive peptides, which enhance the transfection efficiency of PEI/DNA polyplexes in various cell lines.

Genetic Polymorphisms of SP-A, SP-B, and SP-D and Risk of Respiratory Distress Syndrome in Preterm Neonates.

BACKGROUND We examined selected polymorphisms in 3 pulmonary surfactant-associated proteins (SP) for their influence on serum SP levels and risk of respiratory distress syndrome (RDS) in preterm neonates. MATERIAL AND METHODS Premature infants from a Han population were enrolled, including 100 premature infants with RDS (case group) and 120 premature infants without RDS (control group). SNP genotyping for SP-A (+186A/G and +655C/T), SP-B (-18A/C and 1580C/T), and SP-D (Met11ThrT/C and Ala160ThrG/A) used polymerase chain reaction-restriction fragment length polymorphism. Haplotypes were calculated with Shesis software and serum SP-A/B/D levels were quantified by ELISA. RESULTS Case and control groups exhibited significant differences in genotype and allele frequencies of SP-A (+186A/G, +655C/T) and SP-B (1580C/T). However, no statistically significant differences were observed in the allele and genotype frequencies of SP-B -18A/C, SP-D Met11ThrT/C, and SP-D Ala160ThrG/A. Importantly, serum SP-A and SP-B levels were reduced in RDS patients carrying SP-A (+186A/G, +655C/T) and SP-B (1580C/T) polymorphisms. AA genotype of +186A/G, SP-A level, and CC genotype of 1580C/T were independently correlated with increased RDS risk. CONCLUSIONS SP-A (+186A/G) and SP-B (1580C/T) polymorphisms are strongly associated with the risk of RDS in preterm infants. Notably, reduced serum SP-A levels were correlated with a high risk of RDS and may serve as novel biomarkers for RDS detection and monitoring.

High-resolution optogenetics in space and time.

To understand the neural mechanisms of behavior, it is necessary to both monitor and perturb the activity of ensembles of neurons with high specificity. While neural ensemble recordings have been available for decades, progress in high-resolution manipulation techniques has lagged behind. Optogenetics has enabled the manipulation of genetically defined cell types in behaving animals, and recent developments, including multipoint nanofabricated light sources, provide spatiotemporal resolution on a par with that of physiological recordings. Here we review current advances in optogenetic methods for cellular-resolution stimulation and intervention, as well as their integration with real-time neural recordings for closed-loop experimentation. We discuss how these approaches open the door to new kinds of experiments aimed at dissecting the role of specific neural patterns and discrete cellular populations in orchestrating the activity of brain circuits that support behavior and cognition.

Role of surfactant protein C in neonatal genetic disorders of the surfactant system: A case report.

RATIONALE: Respiratory distress syndrome (RDS) refers to the symptoms of progressive dyspnea and respiratory failure in newborns shortly after birth. The clinical and genetic characteristics of patients with neonatal RDS have not been extensively reported. PATIENT CONCERNS: A infant was in critical condition with repeated paroxysmal blood oxygen decline. Oxygen inhalation and noninvasive ventilator-assisted breathing relief were not effective. The etiology was unclear, and there was no family history of lung disease. Surface-active substance replacement therapy and positive pressure-assisted ventilation support were ineffective. DIAGNOSIS: The infant was clinically diagnosed with RDS. Genetic tests revealed a heterozygous missense mutation in the c.168 surfactant protein C (SFTPC) gene. INTERVENTIONS: Tracheal intubation was performed with invasive ventilator-assisted breathing, pulmonary surfactant was administered. Supportive treatment for liver protection and administration of a cardiotonic diuretic, vasodilator, human immunoglobulin (intravenous infusion), fresh frozen plasma, and suspended red blood cells were performed. OUTCOMES: The infant showed poor responses to respiratory and circulatory support, antibiotic treatment, and other treatment methods. The patient was discharged from hospital against the advice of us, cut off from us. The long-term prognosis of the patient after discharge remains unknown. LESSONS: SFTPC gene mutations may be an important risk factor for the development of common lung diseases. Because of the important roles of surfactant functions and metabolism, mutations in these genes can affect the production and function of pulmonary surfactant, leading to severe lung disease in term newborns.

Fundamental Frequency Variation in Crying of Mandarin and German Neonates.

OBJECTIVES: This study examined whether prenatal exposure to either a tonal or a nontonal maternal language affects fundamental frequency (fo) properties in neonatal crying. STUDY DESIGN: This is a population prospective study. PARTICIPANTS: A total of 102 neonates within the first week of life served as the participants. METHODS: Spontaneously uttered cries (N = 6480) by Chinese (tonal language group) and German neonates (nontonal group) were quantitatively analyzed. For each cry utterance, mean fo and four characteristic variation measures (fo range, fo fluctuation, pitch sigma, and pitch sigma fluctuation) were calculated, averaged for individual neonates, and compared between groups. RESULTS: A multiple analysis of variance highlighted a significant multivariate effect for language group: Wilks λ = .76, F(6, 95) = 4.96, P < .0001, ηp2 = .24. Subsequent univariate analyses revealed significant group differences for fo variation measures, with values higher in the tonal language group. The mean fo did not differ between groups. CONCLUSIONS: Data regarding fo variation in infant cries have been suggested as providing critical insight into the maturity of neurophysiological vocal control. Our findings, alongside with auditive perception studies, further underscore the assumption of an early shaping effect of maternal speech, particularly fo-based features, on cry features of newborns. Further studies are needed to reexamine this observation and to assess its potential diagnostic relevance.

Design of an α-helical antimicrobial peptide with improved cell-selective and potent anti-biofilm activity.

AR-23 is a melittin-related peptide with 23 residues. Like melittin, its high α-helical amphipathic structure results in strong bactericidal activity and cytotoxicity. In this study, a series of AR-23 analogues with low amphipathicity were designed by substitution of Ala1, Ala8 and Ile17 with positively charged residues (Arg or Lys) to study the effect of positively charged residue distribution on the biological viability of the antimicrobial peptide. Substitution of Ile17 on the nonpolar face with positively charged Lys dramatically altered the hydrophobicity, amphipathicity, helicity and the membrane-penetrating activity against human cells as well as the haemolytic activity of the peptide. However, substitution on the polar face only slightly affected the peptide biophysical properties and biological activity. The results indicate that the position rather than the number of positively charged residue affects the biophysical properties and selectivity of the peptide. Of all the analogues, A(A1R, A8R, I17K), a peptide with Ala1-Arg, Ala8-Arg and Ile17-Lys substitutions, exhibited similar bactericidal activity and anti-biofilm activity to AR-23 but had much lower haemolytic activity and cytotoxicity against mammalian cells compared with AR-23. Therefore, the findings reported here provide a rationalization for peptide design and optimization, which will be useful for the future development of antimicrobial agents.

Quantitative assessment of the association between the GSTM1-null genotype and the risk of childhood asthma.

BACKGROUND: Many studies investigated the association between the glutathione S-transferase M 1 (GSTM1)-null genotype and childhood asthma risk, but there was obvious inconsistence among those studies. The aim of this meta-analysis was to quantify the strength of association between the GSTM1-null genotype and risk of childhood asthma. METHODS: We searched the PubMed, Embase, and Wangfang databases for studies relating the association between the GSTM1-null genotype and risk of childhood asthma. We estimated the pooled odds ratio (OR) with its 95% confidence interval (95% CI) to assess the association. RESULTS: Nineteen case-control studies with 4,543 childhood asthma cases and 19,394 controls were included into this meta-analysis. Meta-analysis of all 19 studies showed that the GSTM1-null genotype was associated with increased risk of childhood asthma (OR=1.17, 95% CI 1.03-1.34, p=0.017). Subgroup analyses by ethnicity suggested that the GSTM1-null genotype was associated with an increased risk of childhood asthma in Caucasians and Africans (for Caucasians, fixed-effects OR=1.16, 95% CI 1.07-1.27, p=0.001; for Africans, fixed-effects OR=1.92, 95% CI 1.35-2.74, p<0.001). The cumulative meta-analyses showed a trend of obvious association between the GSTM1-null genotype and risk of childhood asthma as information accumulated in the analyses of both total studies and Caucasians. No evidence of publication bias was observed. CONCLUSION: Meta-analyses of available data suggest a significant association between the GSTM1-null genotype and the risk of childhood asthma, and the GSTM1-null genotype contributes to increased risk of childhood asthma, especially in Caucasians and Africans.

[The study on reversing mechanism of multidrug resistance of K562/A02 cell line by curcumin and erythromycin].

OBJECTIVE: To investigate the effects of curcumin (Cur) and erythromycin (EM) on multidrug resistance (MDR) reversal of K562/A02 cell line and their mechanism. METHODS: MTT assay was employed to determine the sensitivity of Cur, EM-treated K562/A02 cells to adriamycin (ADM). Flow cytometry was used to measure intracellular mean fluorescence intensity (MFI) of daunorubicin (DNR). P-gp expression was determined by immunohistochemistry. RT-PCR technique was used to examine the mdr1 mRNA level. RESULTS: IC(50) of ADM in K562/A02 cells was decreased when treated with Cur or EM, and the reversal times (RvT) was 4.9, 3.7 respectively. The RvT reached to 11.3 when treated with Cur (2.5 microg/ml) combined with EM (120 microg/ml). The DNR MFI in K562/A02 cells was significantly lower than that in K562 cells (P < 0.01), and was increased significantly when treated with Cur (2.5 microg/ml) or EM (120 microg/ml) (P < 0.05). There was no significant difference between DNR MFI of K562/A02 cells treated with Cur (2.5 microg/ml) or EM (120 microg/ml). Immunohistochemistry showed that P-gp expression was significantly higher in K562/A02 cells than in K562 cells (P < 0.01), and was reduced in K562/A02 cells treated with each (P < 0.01), though being still higher than that in K562 cells (P < 0.01). P-gp expression of K562/A02 cells treated with each drug for 5 days were lower than that for 3 days (P < 0.01), and lowered further when treated with Cur and EM together (P < 0.01). Mdr1 mRNA level in K562/A02 cells was higher than in K562 cells (P < 0.01), and was decreased when treated with each of the drugs (P < 0.01). The mdr1 mRNA level of K562/A02 cells treated with Cur (2.5 microg/ml) plus EM (120 microg/ml) was decreased most significantly than that treated with other group of drugs. After 5 day treatment the mdr1 mRNA level of K562/A02 cells with Cur (2.5 microg/ml) was lower than that with EM 120 microg/ml (P < 0.01). CONCLUSIONS: Either Cur or EM can partly reverse the multidrug resistance of K562/A02 cells and decrease the expression and function of P-gp in a time-dependent way. MDR reversing effect of Cur combined with EM is stronger than that of Cur or EM alone.