Association between inflammatory markers and frailty in institutionalized older men

Objectives

To determine whether higher serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and high sensitivity C-reactive protein (CRP) were associated with frailty in the older institutionalized men.

Participants

The study enrolled 386 residents from a veterans care home in northern Taiwan in 2007. All participants were men. Residents younger than 65 years or with acute illness were excluded.

Methods

Frailty status was determined based on the frailty phenotype (indicators include weight loss, exhaustion, and low grip strength, slow walking speed). Participants with 3 or more of the indicators were defined as frail, with 1 or 2 as intermediate frail, with no as non-frail. Serum IL-6, TNF-α, and hsCRP levels were measured using enzyme-linked immunosorbent assay and modeled as tertile for severely skewed distributions.

Results

The mean age of the participants was 81.5 ± 4.9 years. The percentages of frail were 33.2%, intermediate frail 59.1% and nonfrail 7.8%. Higher IL-6 level was positively associated with the frail status. Adjusting for age, body mass index, smoking status, and comorbid conditions, serum IL-6 showed significant trend across frailty categories (P = 0.03 [95% CI 1.40–5.24]). No significant associations of TNF-α, and CRP level with frailty were observed. An IL-6 level of 1.79 pg/mL had the optimal predictive value for frailty, with an area under the receiver operating characteristic (ROC) curve of 0.66 (P = 0.01 [95% CI 0.53–0.78]).

Conclusion

Higher serum levels of IL-6 were associated with frailty status in the older institutionalized men with multiple comorbidities.     

Genome-wide high resolution parental-specific DNA and histone methylation maps uncover patterns of imprinting regulation in maize

Genetic imprinting is a specific epigenetic phenomenon in which a subset of genes is expressed depending on their parent-of-origin. Two types of chromatin modifications, DNA methylation and histone modification, are generally believed to be involved in the regulation of imprinting. However, the genome-wide correlation between allele-specific chromatin modifications and imprinted gene expression in maize remains elusive. Here we report genome-wide high resolution allele-specific maps of DNA methylation and histone H3 lysine 27 trimethylation (H3K27me3) in maize endosperm. For DNA methylation, thousands of parent-of-origin dependent differentially methylated regions (pDMRs) were identified. All pDMRs were uniformly paternally hypermethylated and maternally hypomethylated. We also identified 1131 allele-specific H3K27me3 peaks that are preferentially present in the maternal alleles. Maternally expressed imprinted genes (MEGs) and paternally expressed imprinted genes (PEGs) had different patterns of allele-specific DNA methylation and H3K27me3. Allele-specific expression of MEGs was not directly related to allele-specific H3K27me3, and only a subset of MEGs was associated with maternal-specific DNA demethylation, which was primarily located in the upstream and 5′ portion of gene body regions. In contrast, allele-specific expression of a majority of PEGs was related to maternal-specific H3K27me3, with a subgroup of PEGs also associated with maternal-specific DNA demethylation. Both pDMRs and maternal H3K27me3 peaks associated with PEGs are enriched in gene body regions. Our results indicate highly complex patterns of regulation on genetic imprinting in maize endosperm.Genetic imprinting is an epigenetic phenomenon, where genes are expressed in a parent-of-origin dependent manner in many plant species and mammals. Although first discovered in plants (Kermicle and Alleman 1990), research on genetic imprinting is much more advanced in mammals in terms of the number of imprinted genes identified and the understanding of their regulatory mechanisms (Koerner and Barlow 2010; Barlow 2011; Bartolomei and Ferguson-Smith 2011). Only a small number of imprinted genes were observed in plants for a long time since the phenomenon is highly specific to the triploid endosperm (Raissig et al. 2011). However, recent studies have indicated that genetic imprinting in plants is much more prevalent than previously thought, with hundreds of genes shown to be imprinted in several plant species (Gehring et al. 2011; Hsieh et al. 2011; Luo et al. 2011; Waters et al. 2011; Zhang et al. 2011). In contrast to mammals, where the regulation of genetic imprinting has been extensively studied (Koerner and Barlow 2010; Barlow 2011; Abramowitz and Bartolomei 2012), the understanding of regulation of parental imprinting in plants is highly limited.DNA methylation is one of the primary modifications reported to be associated with genetic imprinting. In Arabidopsis, DNA methylation around several maternally expressed imprinted protein-coding genes (MEG) including FWA, FIS2, and MPC was shown to be important for their maternally preferred expression, as all these genes exhibited biallelic expression in endosperm fertilized with met1 pollen (Kinoshita et al. 2004; Jullien et al. 2006; Tiwari et al. 2008). Two studies using RNA-seq in Arabidopsis also showed that a number of MEGs exhibited biallelic expression in paternal met1 endosperm, and the maternal alleles of dozens of paternally expressed imprinted genes (PEGs) were reactivated in maternal dme endosperm (Hsieh et al. 2011; Wolff et al. 2011). In maize, five confirmed endosperm MEGs (Fie1, Fie2, Mez1, Meg1, and Mee1) contain differentially methylated regions (DMRs) (Gutierrez-Marcos et al. 2004; Gutierrez-Marcos et al. 2006; Haun et al. 2007), and activation of the Fie1 maternal allele in the endosperm requires DNA demethylation of the maternal allele (Hermon et al. 2007).Another modification associated with genetic imprinting involves histone methylation. Polycomb repressive complex 2 (PRC2) is known to mediate the trimethylation of histone H3 lysine 27 (H3K27me3) (Schuettengruber and Cavalli 2009). Results on PHE1, the only well-studied PEG in plants, indicated that silencing of its maternal allele depends on a functional PRC2 complex in addition to DNA demethylation (Kohler et al. 2003, 2005; Makarevich et al. 2008). Recently, a number of MEGs and PEGs were shown to be biallelically expressed in maternal fie or fis2 endosperm (Hsieh et al. 2011; Wolff et al. 2011).Although the studies above suggest that DNA methylation and the PRC2 complex could be responsible for monoallelic expression of imprinted genes, there is not yet any general rule for the function of DNA and histone methylation on the regulation of genetic imprinting in plants. A high resolution genome-wide map of allele-specific DNA methylation and allele-specific histone modification will be crucial to gain better understanding of the regulation of genetic imprinting. Recently, several genome-wide studies have provided evidence that allele-specific patterns of DNA methylation or parent-of-origin dependent differentially methylated regions (pDMRs) are associated with some imprinted genes in mice and plants (Zhang et al. 2011; Ibarra et al. 2012; Xie et al. 2012; Rodrigues et al. 2013). Several studies in mammals also suggest a mutually exclusive relationship between allele-specific DNA methylation and histone modification or among different histone modifications (Xin et al. 2001; Fournier et al. 2002; Carr et al. 2007; Lindroth et al. 2008; Singh et al. 2010; Hon et al. 2012).Here we report a genome-wide analysis of allele-specific DMRs, H3K27me3, and imprinted gene expression in maize endosperm. Thousands of pDMRs and allele-specific H3K27me3 peaks were identified. Correlation of pDMRs, allele-specific H3K27me3 profile, and the expression of imprinted genes showed that MEGs and PEGs have different patterns of DNA methylation and H3K27me3. This study reveals complex patterns of genetic imprinting regulation in maize endosperm.     

Cytokine Responses of TNF-α, IL-6, and IL-10 in G6PD-Deficient Infants

G6PD-deficient adults are reported to be susceptible to severe infection, and decreased cytokine responses have been postulated as the underlying mechanism. However, investigating the association of G6PD deficiency and cytokine responses during infancy is lacking. The current study aims to determine whether cytokine responses of tumor necrosis factor ()-α, interleukins (IL)-6, and IL-10 are impaired in the G6PD-deficient infants. Upon agreements with informed consents, peripheral blood mononuclear cells (PBMCs) of enrolled infants were collected twice at 1 month and 1 year of age. PBMCs were then stimulated with toll-like receptor (TLR) agonists—including PAM3csk4 for TLR1–2, poly (I:C) for TLR3, and lipopolysaccharide for TLR4—to analyze the expression of TNF-α, IL-6, and IL-10. Males (P = .004) and phototherapy during neonatal period (P = .008) were more common among G6PD-deficient infants than G6PD-normal subjects. After the stimulation of TLR agonists, there was no significant difference in the expression of TNF-α, IL-6, and IL-10 between PBMCs of G6PD-deficient and -normal infants at both 1 month and 1 year of age. In conclusion, the clinical characteristics of G6PD-deficient infants are different from those of G6PD-normal subjects. The data suggest that the innate immune responses to TLR agonists in G6PD-deficienct infants are not different from those of G6PD-normal infants.     

Mechanistic insight into mineral carbonation and utilization in cement-based materials at solid–liquid interfaces

In order to ensure the viability of CO₂ mineralization and utilization using alkaline solid waste, a mechanistic understanding of reactions at mineral–water interfaces was required to control the reaction pathways and kinetics. In this study, we provided new information for understanding the reactions of CO₂ mineralization and utilization at mineral–water interfaces. Here we have carried out high-energy synchrotron X-ray analyses to characterize the changes of mineral phases in petroleum coke fly ash during CO₂ mineralization and their subsequent utilization as supplementary cementitious materials in cement mortars. The 2-D synchrotron patterns were converted to 1-D diffraction patterns and the results were then interpreted via the Rietveld refinement. The results indicated that there was a continuous source of calcium ions mainly due to the dissolution of CaO and Ca(OH)₂ in fly ash. This would actually enhance the driving force of saturation index at the solid–fluid interfacial layer, and then could eventually result in the nucleation and growth of calcium carbonate (calcite) at the interface. A small quantity of CaSO₄ (anhydrite) in fly ash was also dissolved and simultaneously converted into calcite. In addition, the calcium sulfate in fly ash would effectively prevent the early hydration of tricalcium aluminate in blended cement, and thus could avoid the negative impact on its strength development. The proposed reaction mechanisms were also qualitatively verified by X-ray fluorescence mapping and electron microscopy. These results would help to design efficient reactors and cost-effective processes for CO₂ mineralization and utilization in the future.

Synchrotron-based X-ray analyses for understanding the reactions at mineral–water interfaces for CO₂ mineralization and utilization using petroleum coke fly ash.     

脓毒症线粒体损伤的氧化应激机制及靶向抗氧化剂的研究

线粒体是细胞氧化的重要部位,在脓毒症时氧化应激作为炎症反应最终的结果,可引起线粒体的改变,从而可能导致器官功能损伤。在正常情况下,抗氧化防御系统通过相互作用可以对抗氧化应激,预防对线粒体的损伤。氧化应激在器官功能损伤的过程中起着重要的作用,目前已有研究发现针对线粒体的抗氧化剂靶向治疗可能是脓毒症引起的多器官功能衰竭治疗的一种新策略。该文就氧化应激在脓毒症线粒体损伤机制及靶向抗氧化剂的研究作一综述。     

Benign notochordal cell tumor: a retrospective study of 11 cases with 13 vertebra bodies

Purpose: To analyze the clinical data, MRI, pathological diagnosis, treatment and long-term effects of benign notochordal cell tumor (BNCT), a newly described novel spine tumor. Methods: We retrospectively studied 11 patients’ clinical data of the above. Results: The ratio of males to females was 4:7, and the average age was 49.2 years (range, 18-74 years). Cervical vertebra (5; 38.5%) and thoracic vertebra (5; 38.5%) were the most frequent site followed by the lumbar vertebra (3; 23%). Pain was the main symptom except case 2 who were diagnosed accidently because of prostate cancer. The mean delay from first clinical symptoms to diagnosis was ranged from 2 months to 20 years. MRI showed all BNCTs were osteolytic lesions with hypointense on T1-weighted sequences, hyperintense on T2-weighted sequences. There were 4 vertebral bodies with wedge fracture. There were two cases that had two noncontiguous vertebral bodies with BNCT. In histology, marrow replacement was noted by multivacuolated physaliphorous cells immunoreactive for CK, EMA and S100 protein. All 10 cases except case 2 had vertebral reconstruction and fixation with different methods. Of the 11 patients, 9 had full follow-up data which showed no evidence of recurrence or metastasis without further treatment. Conclusion: Noncontiguous multi-centricity BNCTs are rare. No specific vertebrae are more frequently involved. Once BNCT is diagnosed by pathology, the surgical intervention is necessary for the patients with obvious clinical symptoms although it is benign. There is no evidence of BNCT recurrence or metastasis.     

Protective effects of 2-deoxy-D-glucose on nephrotoxicity induced by cyclosporine A in rats

Objective: This study aims to explore the protective effect mechanism of 2-deoxy-D-glucose on nephrotoxicity of cyclosporin A in vivo. Method: Renal toxicity of SD rats model induced by CsA was established. Serum creatinine, blood urea nitrogen, urine NAG, GSH and MDA were determined and the histopathological changes of rat renal cortex were observed to explore the protective effects of 2-DG on CsA-induced nephrotoxicity. Results: Serum creatinine, BUN and urinary NAG of rats were significantly changed in experimental groups. Pathological results showed that there was obvious renal tubular injury in model group, however, the renal injury was significantly reduced in pre-treated with 2-DG. Conclusions: 2-DG had obvious protective effect on nephrotoxicity especially with high dose. This protective effect could be related to the reduction of ROS induced by CsA. However, 2-DG had no effect on the expression of RIP3.