The Cytokine and Chemokine Profiles in Patients with Hand,Foot and Mouth Disease of Different Severities in Shanghai,China, 2010

Background and purpose

Systemic upregulation of inflammatory cytokines is characteristic of critical severe hand, foot, and mouth disease (HFMD) with pulmonary edema. Thus, immunomodulatory medicines such as steroids, including methylprednisolone, have been proposed to treat patients with severe HFMD in China, because it is postulated that inflammatory cytokines play a role in the development of severe complications. This study is to further investigate the inflammatory response in the relatively mild HFMD patients, and whether steroid treatment has a beneficial effect on the suppression of inflammation in HFMD patients.

Method

We measured the levels of 50 kinds of chemokines, cytokines, growth factors and soluble receptors in serum samples from control patients without HFMD and the HFMD patients with or without prior treatment of intravenous methylprednisolone.

Results

Our present study found that even relatively mild HFMD patients without central nervous system (CNS) complications had elevated serum levels of inflammatory cytokines, including interleukin (IL)-3, IL-6, IL-12p40, and tumor necrosis factor (TNF)-α, which suggested systemic inflammation. In contrast, these patients also have decreased levels of other serum biomarkers, including IL-1Ra, IL-8, IL-16, soluble ICAM-1, CXCL-1, and CCL27. The dysregulation of cytokine and chemokine expression may be involved in CNS complications and unbalanced circulating leukocytes in HFMD patients. Surprisingly, patients treated with methylprednisolone had no difference in the expression levels of HFMD-associated biomarkers instead had slightly increased levels of IL-17A, which was not associated with the occurrence of HFMD.

Conclusion

Whether steroid treatment has any beneficial effect on the prognosis of HFMD patients requires to be further investigated.     

Circulating Lipocalin-2 and Retinol-Binding Protein 4 Are Associated with Intima-Media Thickness and Subclinical Atherosclerosis in Patients with Type 2 Diabetes

Background

The lipocalin family proteins, including lipocalin-2 and retinol-binding protein 4 (RBP4), are adipokines closely associated with obesity-related metabolic disorders. In this study, we evaluated the association of serum lipocalin-2 and RBP4 with intima-media thickness (IMT) and subclinical atherosclerosis in type 2 diabetic patients.

Methods and Results

Serum levels of lipocalin-2 and RBP4 were measured in 284 type 2 diabetic patients. Subclinical atherosclerosis was assessed by IMT at carotid, femoral and iliac arteries with ultrasound. Patients with subclinical atherosclerosis showed significantly higher circulating concentrations of lipocalin-2 and RBP4 when compared to those without [112.9 (86.4 to 202.1) µg/L versus 77.2(55.0–150.4) µg/L, 37.1(32.3–40.8) mg/L versus 23.2(20.1–29.2) mg/L, respectively; P = 0.002, P<0.001, respectively]. Moreover, positive correlations were observed between carotid IMT and lipocalin-2 (r = 0.170, P = 0.018) or RBP4 (r = 0.132, P = 0.040), femoral IMT and lipocalin-2 (r = 0.160, P = 0.027), as well as between iliac IMT and RBP4 (r = 0.241, P<0.001). Multiple logistic regression analysis further demonstrated that these two adipokines were independent risk factors for subclinical atherosclerosis in type 2 diabetes.

Conclusion

Circulating levels of lipocalin-2 and RBP4 are positively correlated with carotid IMT and subclinical atherosclerosis in type 2 diabetes, which suggests a potential role of these two lipid-binding chaperones in the pathogenesis of vascular complications of diabetes.     

Polymorphisms in the mTOR Gene and Risk of Sporadic Prostate Cancer in an Eastern Chinese Population

Background

The mTOR gene regulates cell growth by controlling mRNA translation, ribosome biogenesis, autophagy, and metabolism. Abnormally increased expression of mTOR was associated with carcinogenesis, and its functional single nucleotide polymorphisms (SNPs) may regulate the expression of mTOR and thus contribute to cancer risk.

Methodology/Principal Findings

In a hospital-based case-control study of 1004 prostate cancer (PCa) cases and 1051 cancer-free controls, we genotyped six potentially functional SNPs of mTOR (rs2536 T>C, rs1883965 G>A, rs1034528 G>C, rs17036508 T>C, rs3806317 A>G, and rs2295080 T>G) and assessed their associations with risk of PCa by using logistic regression analysis.

Conclusions/Significances

In the single-locus analysis, we found a significantly increased risk of PCa associated with mTOR rs2536 CT/CC and rs1034528 CG/CC genotypes [adjusted OR = 1.42 (1.13–1.78), P = 0.003 and 1.29 (1.07–1.55), P = 0.007), respectively], compared with their common homozygous genotypes, whereas mTOR rs2295080 GT/GG genotypes were associated with a decreased risk of PCa [adjusted OR = 0.76 (0.64–0.92), P = 0.003], compared with wild-type TT genotypes. In the combined analysis of the six SNPs, we found that individuals carrying two or more adverse genotypes had an increased risk of PCa [adjusted OR = 1.24 (1.04–1.47), P = 0.016], compared with individuals carrying less than two adverse genotypes. In the multiple dimension reduction analysis, body mass index (BMI) was the best one-factor model with the highest CVC (100%) and the lowest prediction error (42.7%) among all seven factors. The model including an interaction among BMI, rs17036508, and rs2536 was the best three-factor model with the highest CVC (100%) and the lowest prediction error of 41.9%. These findings suggested that mTOR SNPs may contribute to the risk of PCa in Eastern Chinese men, but the effect was weak and needs further validation by larger population-based studies.     

Ecosystem Health Assessment in the Pearl River Estuary of China by Considering Ecosystem Coordination

Marine ecosystem is a complex nonlinear system. However, ecosystem health assessment conventionally builds on a linear superposition of changes in ecosystem components and probably fails to evaluate nonlinear interactions among various components. To better reflect the intrinsic interactions and their impacts on ecosystem health, an ecosystem coordination index, defined as the matching level of ecosystem structure/services, is proposed and incorporated into the ecosystem health index for a systematic diagnosis in the Pearl River Estuary, China. The analysis results show that the ecosystem health index over the last three decades decreased from 0.91 to 0.50, indicating deteriorating from healthy to unhealthy status. The health index is 3–16% lower than that calculated using the common method without considering ecosystem coordination. Ecosystem health degradation in the Pearl River Estuary manifested as significant decreases in structure/services and somewhat mismatching among them. Overall, the introduction of coordination in ecosystem health assessment could improve the understanding of the mechanism of marine ecosystem change and facilitate effective restoration of ecosystem health.     

Bone Mineral Density of the Spine in 11,898 Chinese Infants and Young Children: A Cross-Sectional Study

Background

Bone mineral density (BMD) increases progressively during childhood and adolescence and is affected by various genetic and environmental factors. The aim of this study was to establish reference values for lumbar BMD in healthy Chinese infants and young children and investigate its influencing factors.

Methods and Findings

Healthy children aged 0 to 3 years who underwent regular physical examinations at the Child Health Care Clinic of Hubei Maternal and Child Health Hospital (N = 11,898) were recruited for this study. We also chose 379 preterm infants aged 0 to 1 years to preliminarily explore the development of BMD in this special population. BMD (g/cm²) measurements of the lumbar spine (L2–L4) were carried out with dual-energy X-ray absorptiometry and a questionnaire was administered to full-term children''s parents to gather information on various nutritional and lifestyle factors as well as mothers'' nutritional supplement use during pregnancy. Lumbar BMD significantly increased with age among both boys and girls (p<0.05), with fastest growth observed during the first postnatal year. There was no significant difference in lumbar BMD between boys and girls of similar age (p>0.05), either among healthy reference children or preterm infants. However, BMD values in preterm infants were significantly lower than those in term infants 3 to 8 months old (p<0.05) after adjustment for gestational age. Multivariable linear regression analysis indicated significant positive associations between lumbar BMD of healthy children and the child''s age and current weight, mother''s weight gain during pregnancy, birth weight, children''s outdoor activity duration and children''s physical activity duration.

Conclusion

Our study provides reference values of lumbar BMD for healthy Chinese children aged 0 to 3 years and identifies several influencing factors.     

Isolation and Identification of a Novel Antifungal Protein from a Rhizobacterium Bacillus subtilis Strain F3

Bacillus subtilis strain F3, isolated from peach rhizosphere soil, is an antifungal bacterium against many plant pathogens. In this study, the antifungal protein was isolated and purified by ammonium sulphate and chromatography, then identified by mass spectrum analysis. By sequential chromatography of Sephadex G‐50, DEAE‐Sephadex A‐25 anion exchange and Sephadex G‐100, a fraction designated as F3A was isolated to show a single protein band in SDS‐PAGE and be antagonistic towards Monilinia fructicola. The peptide mass fingerprinting of the protein band of F3A had high similarity with the amino acid sequences of several flagellin protein of B. subtilis. There were seven amino acid fragments matched with the protein having the highest score, and sequence coverage was 33%. F3A showed a strongly inhibitory effect to the growth and sporulation of M. fructicola. There were little aerial hyphae and conidia at the antifungal zone, and the hyphae were abnormal with some cell wall collapse and several vacuoles in cells.     

Metabolic signatures of esophageal cancer: NMR-based metabolomics and UHPLC-based focused metabolomics of blood serum

Focused metabolic profiling is a powerful tool for the determination of biomarkers. Here, a more global proton nuclear magnetic resonance (¹H NMR)-based metabolomic approach coupled with a relative simple ultra high performance liquid chromatography (UHPLC)-based focused metabolomic approach was developed and compared to characterize the systemic metabolic disturbances underlying esophageal cancer (EC) and identify possible early biomarkers for clinical prognosis. Serum metabolic profiling of patients with EC (n = 25) and healthy controls (n = 25) was performed by using both ¹H NMR and UHPLC, and metabolite identification was achieved by multivariate statistical analysis. Using orthogonal projection to least squares discriminant analysis (OPLS-DA), we could distinguish EC patients from healthy controls. The predictive power of the model derived from the UHPLC-based focused metabolomics performed better in both sensitivity and specificity than the results from the NMR-based metabolomics, suggesting that the focused metabolomic technique may be of advantage in the future for the determination of biomarkers. Moreover, focused metabolic profiling is highly simple, accurate and specific, and should prove equally valuable in metabolomic research applications. A total of nineteen significantly altered metabolites were identified as the potential disease associated biomarkers. Significant changes in lipid metabolism, amino acid metabolism, glycolysis, ketogenesis, tricarboxylic acid (TCA) cycle and energy metabolism were observed in EC patients compared with the healthy controls. These results demonstrated that metabolic profiling of serum could be useful as a screening tool for early EC diagnosis and prognosis, and might enhance our understanding of the mechanisms involved in the tumor progression.     

腐植酸对高温胁迫下掌叶半夏生长生理特性及块茎次生代谢的影响

采用不同浓度(0、20、40、60、80、100mg/L)腐植酸(HA)叶面喷施处理,通过盆栽实验分析了HA对高温胁迫下掌叶半夏幼苗生长生理指标及次生代谢的调控效应。结果显示:(1)各浓度HA处理均可不同程度地促进高温胁迫下掌叶半夏的生长发育,且以80mg/L HA处理下其块茎鲜重(6.990 5g/株)、叶柄鲜重(1.755 4g/株)及总叶绿素含量(19.961 3mg/g)最高,较对照分别显著提高21.25%、118.5%和37.19%。(2)当HA处理浓度为60mg/L时,掌叶半夏幼苗叶片中可溶性糖、可溶性蛋白含量均最高,分别比对照显著提高66.67%、40.91%;叶片抗氧化酶(SOD、POD)活性达到最大值,MDA含量降至最低,SOD、POD活性分别比对照显著提高818.98%和48.2%,MDA含量较对照显著降低62.08%;且块茎中鸟苷含量较高,比对照显著提高52.94%。(3)当叶面喷施80mg/L HA时,掌叶半夏幼苗叶片中游离脯氨酸含量和块茎中总生物碱、总有机酸、腺苷的含量均最高,分别比对照显著提高169.63%、27.19%、42.32%、96.23%。研究表明,适宜浓度HA处理可显著提高高温胁迫下掌叶半夏幼苗叶片内抗氧化酶(SOD、POD)的活性及渗透调节物质(可溶性糖、可溶性蛋白、游离脯氨酸)含量,以及块茎中次生代谢产物(总生物碱、总有机酸、鸟苷和腺苷)的含量,有效减轻夏季高温对掌叶半夏幼苗叶片的伤害、延缓衰老、提高其幼苗抗热性,促进生长、延长生长期。