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1.  Association of CKD-MBD Markers with All-Cause Mortality in Prevalent Hemodialysis Patients: A Cohort Study in Beijing 
PLoS ONE  2017;12(1):e0168537.
The relationships between all-cause mortality and serum intact parathyroid hormone (iPTH), calcium, and phosphate are fairly diverse in patients on maintenance hemodialysis according to prior studies. This study evaluated the association of chronic kidney disease-mineral and bone disorder (CKD-MBD) markers with all-cause mortality in prevalent hemodialysis patients from 2007 to 2012 in Beijing, China. A cohort, involving 8530 prevalent hemodialysis patients who had undergone a 6–70 months follow-up program (with median as 40 months) was formed. Related data was recorded from the database in 120 hemodialysis centers of Beijing Health Bureau (2007 to 2012). Information regarding baseline demographics, blood CKD-MBD markers and all-cause mortality was retrospectively reviewed. By using multivariate Cox regression model analysis, patients with a low iPTH level at baseline were found to have greater risk of mortality (<75pg/ml, HR = 1.36, 95% confidence interval (CI) 1.16–1.60) than those with a baseline iPTH level within 150–300 pg/ml. Similarly, death risk showed an increase when the baseline serum calcium presented a low level (<2.1mmol/L, HR = 1.54; 95% CI 1.37–1.74). Levels of baseline serum phosphorus were not associated with the risk of death. Similar results appeared through the baseline competing risks regression analysis. Patients with a lower level of serum iPTH or calcium are at a higher risk of all-cause mortality compared with those within the range recommended by Kidney Disease Outcome Quality Initiative (KDOQI) guidelines.
doi:10.1371/journal.pone.0168537
PMCID: PMC5207661  PMID: 28045985
2.  Redox Mechanism of Reactive Oxygen Species in Exercise 
It is well known that regular exercise can benefit health by enhancing antioxidant defenses in the body. However, unaccustomed and/or exhaustive exercise can generate excessive reactive oxygen species (ROS), leading to oxidative stress-related tissue damages and impaired muscle contractility. ROS are produced in both aerobic and anaerobic exercise. Mitochondria, NADPH oxidases and xanthine oxidases have all been identified as potential contributors to ROS production, yet the exact redox mechanisms underlying exercise-induced oxidative stress remain elusive. Interestingly, moderate exposure to ROS is necessary to induce body's adaptive responses such as the activation of antioxidant defense mechanisms. Dietary antioxidant manipulation can also reduce ROS levels and muscle fatigue, as well as enhance exercise recovery. To elucidate the complex role of ROS in exercise, this review updates on new findings of ROS origins within skeletal muscles associated with various types of exercises such as endurance, sprint and mountain climbing. In addition, we will examine the corresponding antioxidant defense systems as well as dietary manipulation against damages caused by ROS.
doi:10.3389/fphys.2016.00486
PMCID: PMC5097959  PMID: 27872595
dietary antioxidant; exercise; exercise-induced adaptation; ROS; skeletal muscle
3.  The Expression and Clinical Outcome of pCHK2-Thr68 and pCDC25C-Ser216 in Breast Cancer 
Checkpoint kinase 2 (CHK2) and cell division cycle 25C (CDC25C) are two proteins involved in the DNA damage response pathway, playing essential roles in maintaining genome integrity. As one of the major hallmarks of abnormal cellular division, genomic instability occurs in most cancers. In this study, we identified the functional expression of pCHK2-Thr68 and pCDC25C-Ser216 in breast cancer, as well as its association with breast cancer survival. Tissue microarray analysis using immunohistochemistry was constructed to identify the expression of pCHK2-Thr68 and pCDC25C-Ser216 in 292 female breast cancer patients. The relationship among protein expression, clinicopathological factors (e.g., human epidermal growth factor receptor 2 (HER 2), tumor size, tumor-node-metastasis (TNM) classification), and overall survival of the breast cancer tissues were analyzed using Pearson’s χ-square (χ2) test, Fisher’s exact test, multivariate logistic regression and Kaplan–Meier survival analysis. Significantly higher expressions of pCHK2-Thr68 and pCDC25C-Ser216 were observed in the nucleus of the breast cancer cells compared to the paracancerous tissue (pCHK2-Thr68, 20.38% vs. 0%; pCDC25C-Ser216, 82.26% vs. 24.24%). The expression of pCHK2-Thr68 and pCDC25C-Ser216 in breast cancer showed a positive linear correlation (p = 0.026). High expression of pCHK2-Thr68 was associated with decreased patient survival (p = 0.001), but was not an independent prognostic factor. Our results suggest that pCHK2-Thr68 and pCDC25C-Ser216 play important roles in breast cancer and may be potential treatment targets.
doi:10.3390/ijms17111803
PMCID: PMC5133804  PMID: 27801830
pCHK2-Thr68; pCDC25C-Ser216; immunohistochemistry; breast cancer; genomic instability
4.  Comparison of High-Protein, Intermittent Fasting Low-Calorie Diet and Heart Healthy Diet for Vascular Health of the Obese 
Aim: It has been debated whether different diets are more or less effective in long-term weight loss success and cardiovascular disease prevention among men and women. To further explore these questions, the present study evaluated the combined effects of a high-protein, intermittent fasting, low-calorie diet plan compared with a heart healthy diet plan during weight loss, and weight loss maintenance on blood lipids and vascular compliance of obese individuals.
Methods: The experiment involved 40 obese adults (men, n = 21; women, n = 19) and was divided into two phases: (a) 12-week high-protein, intermittent fasting, low-calorie weight loss diet comparing men and women (Phase 1) and (b) a 1-year weight maintenance phase comparing high-protein, intermittent fasting with a heart healthy diet (Phase 2). Body weight, body mass index (BMI), blood lipids, and arterial compliance outcomes were assessed at weeks 1 (baseline control), 12 (weight loss), and 64 (12 + 52 week; weight loss maintenance).
Results: At the end of weight loss intervention, concomitant reductions in body weight, BMI and blood lipids were observed, as well as enhanced arterial compliance. No sex-specific differences in responses were observed. During phase 2, the high-protein, intermittent fasting group demonstrated a trend for less regain in BMI, low-density lipoprotein (LDL), and aortic pulse wave velocity than the heart healthy group.
Conclusion: Our results suggest that a high-protein, intermittent fasting and low-calorie diet is associated with similar reductions in BMI and blood lipids in obese men and women. This diet also demonstrated an advantage in minimizing weight regain as well as enhancing arterial compliance as compared to a heart healthy diet after 1 year.
doi:10.3389/fphys.2016.00350
PMCID: PMC5002412  PMID: 27621707
arterial compliance; cholesterol; lipids; weight loss; weight relapse
5.  Paeonol Protects Rat Heart by Improving Regional Blood Perfusion during No-Reflow 
No-reflow phenomenon, defined as inadequate perfusion of myocardium without evident artery obstruction, occurs at a high incidence after coronary revascularization. The mechanisms underlying no-reflow is only partially understood. It is commonly caused by the swelling of endothelial cells, neutrophil accumulation, and vasoconstriction, which are all related to acute inflammation. Persistent no-reflow can lead to hospitalization and mortality. However, an effective preventive intervention has not yet been established. We have previously found that paeonol, an active extraction from the root of Paeonia suffruticosa, can benefit the heart function by inhibiting tissue damage after ischemia, reducing inflammation, and inducing vasodilatation. To further investigate the potential cardioprotective action of paeonol on no-reflow, healthy male Wistar rats were randomly divided into four groups: sham, ischemia-reperfusion (I/R) injury (left anterior descending coronary artery was ligated for 4 h followed by reperfusion for 8 h), and I/R injury pretreated with paeonol at two different doses. Real-time myocardial contrast echocardiography was used to monitor regional blood perfusion and cardiac functions. Our data indicated that paeonol treatment significantly reduces myocardial infarct area and no-reflow area (n = 8; p < 0.05). Regional myocardial perfusion (A·β) and cardiac functions such as ejection fraction, stroke volume, and fractional shortening were elevated by paeonol (n = 8; p < 0.05). Paeonol also lowered the serum levels of lactate dehydrogenase, creatine kinase, cardiac troponin T, and C-reactive protein, as indices of myocardial injury. Paeonol exerts beneficial effects on attenuating I/R-associated no-reflow injuries, and may be considered as a potential preventive treatment for cardiac diseases or post-coronary revascularization in which no-reflow often occurs.
doi:10.3389/fphys.2016.00298
PMCID: PMC4954854  PMID: 27493631
paeonol; myocardial injury; no-reflow; infarct size; rat
6.  Reactive oxygen species formation and bystander effects in gradient irradiation on human breast cancer cells 
Oncotarget  2016;7(27):41622-41636.
Ionizing radiation (IR) in cancer radiotherapy can induce damage to neighboring cells via non-targeted effects by irradiated cells. These so-called bystander effects remain an area of interest as it may provide enhanced efficacy in killing carcinomas with minimal radiation. It is well known that reactive oxygen species (ROS) are ubiquitous among most biological activities. However, the role of ROS in bystander effects has not been thoroughly elucidated. We hypothesized that gradient irradiation (GI) has enhanced therapeutic effects via the ROS-mediated bystander pathways as compared to uniform irradiation (UI). We evaluated ROS generation, viability, and apoptosis in breast cancer cells (MCF-7) exposed to UI (5 Gy) or GI (8–2 Gy) in radiation fields at 2, 24 and 48 h after IR. We found that extracellular ROS release induced by GI was higher than that by UI at both 24 h (p < 0.001) and 48 h (p < 0.001). More apoptosis and less viability were observed in GI when compared to UI at either 24 h or 48 h after irradiation. The mean effective doses (ED) of GI were ~130% (24 h) and ~48% (48 h) higher than that of UI, respectively. Our results suggest that GI is superior to UI regarding redox mechanisms, ED, and toxic dosage to surrounding tissues.
doi:10.18632/oncotarget.9517
PMCID: PMC5173083  PMID: 27223435
bystander effects; reactive oxygen species; gradient irradiation; breast cancer cells; MCF-7
7.  Anemia Management in the China Dialysis Outcomes and Practice Patterns Study 
Blood purification  2016;42(1):33-43.
Background
As the utilization of hemodialysis increases in China, it is critical to examine anemia management.
Methods
Using data from the China Dialysis Outcomes and Practice Patterns Study (DOPPS), we describe hemoglobin (Hgb) distribution and anemia-related therapies.
Results
Twenty one percent of China's DOPPS patients had Hgb <9 g/dl, compared with ≤ 10% in Japan and North America. A majority of medical directors targeted Hgb ≥ 11. Patients who were female, younger, or recently hospitalized had higher odds of Hgb <9; those with insurance coverage or on twice weekly dialysis had lower odds of Hgb <9. Iron use and erythropoietin-stimulating agents (ESAs) dose were modestly higher for patients with Hgb <9 compared with Hgb in the range 10–12.
Conclusion
A large proportion of hemodialysis patients in China's DOPPS do not meet the expressed Hgb targets. Less frequent hemodialysis, patient financial contribution, and lack of a substantial increase in ESA dose at lower Hgb concentrations may partially explain this gap. Video Journal Club ‘Cappuccino with Claudio Ronco’ at http://www.karger.com/?doi=442741.
doi:10.1159/000442741
PMCID: PMC4919113  PMID: 27045519
China; Domestic erythropoietin stimulating agents; End-stage renal disease-related anemia; Intravenous iron
8.  Copper Deficiency in the Lungs of TNF-α Transgenic Mice 
Tumor necrosis factor (TNF)-α is a well-known pro-inflammatory cytokine. Increased expression of Tnf-α is a feature of inflammatory lung diseases, such as asthma, emphysema, fibrosis, and smoking-induced chronic obstructive pulmonary disease (COPD). Using a mouse line with lung-specific Tnf-α overexpression (SPC-TNF-α) to mimic TNF-α-associated lung diseases, we investigated the role of chronic inflammation in the homeostasis of lung trace elements. We performed a quantitative survey of micronutrients and biometals, including copper (Cu), zinc (Zn), and selenium (Se), in the transgenic mice tissues. We also examined the expression of Cu-dependent proteins in the inflammatory lung tissue to determine whether they were affected by the severe Cu deficiency, including cuproenzymes, Cu transporters, and Cu chaperones. We found consistent lung-specific reduction of the metal Cu, with a mean decrease of 70%; however, Zn and Se were unaffected in all other tissues. RT-PCR showed that two Cu enzymes associated with lung pathology were downregulated: amine oxidase, Cu containing 3 (Aoc3) and lysyl oxidase (Lox). Two factors, vascular endothelial growth factor (Vegf) and focal adhesion kinase (Fak), related with Cu deficiency treatment, showed decreased expression in the transgenic inflammatory lung. We concluded that Cu deficiency occurs following chronic TNF-α-induced lung inflammation and this likely plays an essential role in the inflammation-induced lung damage. These results suggest the restoration of lung Cu status as a potential strategy in both treatment and prevention of chronic lung inflammation and related disorders.
doi:10.3389/fphys.2016.00234
PMCID: PMC4906028  PMID: 27378943
biometals; COPD; inflammation; micronutrients; oxidative stress
9.  Role and Mechanism of Microglial Activation in Iron-Induced Selective and Progressive Dopaminergic Neurodegeneration 
Molecular neurobiology  2013;49(3):1153-1165.
Parkinson’s disease (PD) patients have excessive iron depositions in substantia nigra (SN). Neuroinflammation characterized by microglial activation is pivotal for dopaminergic neurodegeneration in PD. However, the role and mechanism of microglial activation in iron-induced dopaminergic neurodegeneration in SN remain unclear yet. This study aimed to investigate the role and mechanism of microglial β-nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) activation in iron-induced selective and progressive dopaminergic neurodegeneration. Multiple primary midbrain cultures from rat, NOX2+/+ and NOX2−/− mice were used. Dopaminergic neurons, total neurons, and microglia were visualized by immunostainings. Cell viability was measured by MTT assay. Superoxide (O2·−) and intracellular reactive oxygen species (iROS) were determined by measuring SOD-inhibitable reduction of tetrazolium salt WST-1 and DCFH-DA assay. mRNA and protein were detected by real-time PCR and Western blot. Iron induces selective and progressive dopaminergic neurotoxicity in rat neuron–microglia–astroglia cultures and microglial activation potentiates the neurotoxicity. Activated microglia produce a magnitude of O2·− and iROS, and display morphological alteration. NOX2 inhibitor diphenylene iodonium protects against iron-elicited dopaminergic neurotoxicity through decreasing microglial O2·− generation, and NOX2−/− mice are resistant to the neurotoxicity by reducing microglial O2·− production, indicating that iron-elicited dopaminergic neurotoxicity is dependent of NOX2, a O2·−-generating enzyme. NOX2 activation is indicated by the increased mRNA and protein levels of subunits P47 and gp91. Molecules relevant to NOX2 activation include PKC-σ, P38, ERK1/2, JNK, and NF-ΚBP65 as their mRNA and protein levels are enhanced by NOX2 activation. Iron causes selective and progressive dopaminergic neurodegeneration, and microglial NOX2 activation potentiates the neurotoxicity. PKC-σ, P38, ERK1/2, JNK, and NF-ΚBP65 are the potential molecules relevant to microglial NOX2 activation.
doi:10.1007/s12035-013-8586-4
PMCID: PMC4878835  PMID: 24277523
Dopaminergic neurodegeneration; Iron; Microglial activation; Neuroinflammation; β-nicotinamide adenine dinucleotide phosphate oxidase 2; Parkinson’s disease; Mechanism
10.  Identification and functional characterization of the sulfate transporter gene GmSULTR1;2b in soybean 
BMC Genomics  2016;17:373.
Background
Soybean is a major source of oil and protein in the human diet and in animal feed. However, as soybean is deficient in sulfur-containing amino acids, its nutritional value is limited. Increasing sulfate assimilation and utilization efficiency is a valuable approach to augment the concentration of sulfur-containing amino acids in soybean seeds, and sulfate transporters play important roles in both sulfate uptake and translocation within plants.
Results
In this study, we isolated and characterized a soybean sulfate transporter gene: GmSULTR1;2b. The gene was found to be specifically expressed in root tissues and induced by low-sulfur stress. In addition, GmSULTR1;2b expression in yeast could complement deficiency in the sulfate transporter genes SUL1 and SUL2. Under +S conditions, GmSULTR1;2b-overexpressing tobacco plants accumulated higher levels of organic matter and exhibited enhanced biomass and seed weight compared to control plants. Under -S conditions, acclimation of GmSULTR1;2b-overexpressing plants was much better than control plants. GmSULTR1;2b-overexpressing tobacco seedlings showed better tolerance to drought stress than the control plants, but no significant difference was observed under salt stress. Transcriptome analysis revealed 515 genes with at least a 2-fold change in expression in the leaves of tobacco plants overexpressing GmSULTR1;2b. Of these, 227 gene annotations were classified into 12 functional categories associated with 123 relevant pathways, including biosynthesis and metabolism-related proteins, stress-related proteins, and transporters.
Conclusions
The findings reported here indicate that the increased biomass and seed yield observed in transgenic tobacco plants could have resulted from greater nutrient uptake and transport capability as well as enhanced development and accumulation of organic matter. Taken together, our results indicate that GmSULTR1;2b plays an important role in sulfur uptake and could alter the sulfur status of plants. Our study suggests that overexpressing GmSULTR1;2b may enhance plant yield under +S conditions, reduce plant production loss under -S conditions, and improve plant tolerance to sulfur deficiency stress.
Electronic supplementary material
The online version of this article (doi:10.1186/s12864-016-2705-3) contains supplementary material, which is available to authorized users.
doi:10.1186/s12864-016-2705-3
PMCID: PMC4874011  PMID: 27206527
Soybean; Sulfate transporter; GmSULTR1;2b; Low-sulfur stress; Sulfate uptake
11.  Characterization and redox mechanism of asthma in the elderly 
Oncotarget  2016;7(18):25010-25021.
Asthma is a chronic disease characterized by reversible airflow limitation, coughing, bronchial constriction, and an inflammatory immune response. While asthma has frequently been categorized as emerging in childhood, evidence has begun to reveal that the elderly population is certainly susceptible to late-onset, or even long-standing asthma. Non-atopic asthma, most commonly found in elderly patients is associated with elevated levels of serum and sputum neutrophils and may be more detrimental than atopic asthma. The mortality of asthma is high in the elderly since these patients often possess more severe symptoms than younger populations. The redox mechanisms that mediate inflammatory reactions during asthma have not been thoroughly interpreted in the context of aging. Thus, we review the asthmatic symptoms related to reactive oxygen species (ROS) and reactive nitrogen species (RNS) in seniors. Moreover, immune status in the elderly is weakened in part by immunosenescence, which is broadly defined as the decline in functionality of the immune system that corresponds with increasing age. The effects of immunosenescence on the expression of biomarkers potentially utilized in the clinical diagnosis of asthma remain unclear. It has also been shown that existing asthma treatments are less effective in the elderly. Thus, it is necessary that clinicians approach the diagnosis and treatment of asthmatic senior patients using innovative methods. Asthma in the elderly demands more intentional diagnostic and therapeutic research since it is potentially one of the few causes of mortality and morbidity in the elderly that is largely reversible.
doi:10.18632/oncotarget.7075
PMCID: PMC5041886  PMID: 26843624
aging; allergic; inflammation; oxidative stress; respiratory
12.  Unfractionated Heparin Promotes Osteoclast Formation in Vitro by Inhibiting Osteoprotegerin Activity 
Heparin has been proven to enhance bone resorption and induce bone loss. Since osteoclasts play a pivotal role in bone resorption, the effect of heparin on osteoclastogenesis needs to be clarified. Since osteocytes are the key modulator during osteoclastogenesis, we evaluated heparin’s effect on osteoclastogenesis in vitro by co-culturing an osteocyte cell line (MLO-Y4) and pre-osteoclasts (RAW264.7). In this co-culture system, heparin enhanced osteoclastogenesis and osteoclastic bone resorption while having no influence on the production of RANKL (receptor activator of NFκB ligand), M-CSF (macrophage colony-stimulating factor), and OPG (osteoprotegerin), which are three main regulatory factors derived from osteocytes. According to previous studies, heparin could bind specifically to OPG and inhibit its activity, so we hypothesized that this might be a possible mechanism of heparin activity. To test this hypothesis, osteoclastogenesis was induced using recombinant RANKL or MLO-Y4 supernatant. We found that heparin has no effect on RANKL-induced osteoclastogenesis (contains no OPG). However, after incubation with OPG, the capacity of MLO-Y4 supernatant for supporting osteoclast formation was increased. This effect disappeared after OPG was neutralized and reappeared after OPG was replenished. These results strongly suggest that heparin promotes osteocyte-modulated osteoclastogenesis in vitro, at least partially, through inhibiting OPG activity.
doi:10.3390/ijms17040613
PMCID: PMC4849062  PMID: 27110777
unfractionated heparin; osteocyte; osteoclast; osteoclastogenesis; osteoprotegerin (OPG)
13.  Redox Characterization of Functioning Skeletal Muscle 
Skeletal muscle physiology is influenced by the presence of chemically reactive molecules such as reactive oxygen species (ROS). These molecules regulate multiple redox-sensitive signaling pathways that play a critical role in cellular processes including gene expression and protein modification. While ROS have gained much attention for their harmful effects in muscle fatigue and dysfunction, research has also shown ROS to facilitate muscle adaptation after stressors such as physical exercise. This manuscript aims to provide a comprehensive review of the current understanding of redox signaling in skeletal muscle. ROS-induced oxidative stress and its role in the aging process are discussed. Mitochondria have been shown to generate large amounts of ROS during muscular contractions, and thus are susceptible to oxidative stress. ROS can modify proteins located in the mitochondrial membrane leading to cell death and osmotic swelling. ROS also contribute to the necrosis and inflammation of muscle fibers that is associated with muscular diseases including Duchenne muscular dystrophy. It is imperative that future research continues to investigate the exact role of ROS in normal skeletal muscle function as well as muscular dysfunction and disease.
doi:10.3389/fphys.2015.00338
PMCID: PMC4649055  PMID: 26635624
atrophy; redox; signaling; disease; oxidative stress
14.  Molecular Regulation of Toll-like Receptors in Asthma and COPD 
Asthma and chronic obstructive pulmonary disease (COPD) have both been historically associated with significant morbidity and financial burden. These diseases can be induced by several exogenous factors, such as pathogen-associated molecular patterns (PAMPs) (e.g., allergens and microbes). Endogenous factors, including reactive oxygen species, and damage-associated molecular patterns (DAMPs) recognized by toll-like receptors (TLRs), can also result in airway inflammation. Asthma is characterized by the dominant presence of eosinophils, mast cells, and clusters of differentiation (CD)4+ T cells in the airways, while COPD typically results in the excessive formation of neutrophils, macrophages, and CD8+ T cells in the airways. In both asthma and COPD, in the respiratory tract, TLRs are the primary proteins of interest associated with the innate and adaptive immune responses; hence, multiple treatment options targeting TLRs are being explored in an effort to reduce the severity of the symptoms of these disorders. TLR-mediated pathways for both COPD and asthma have their similarities and differences with regards to cell types and the pro-inflammatory cytotoxins present in the airway. Because of the complex TLR cascade, a variety of treatments have been used to minimize airway hypersensitivity and promote bronchodilation. Although unsuccessful at completely alleviating COPD and severe asthmatic symptoms, new studies are focused on possible targets within the TLR cascade to ameliorate airway inflammation.
doi:10.3389/fphys.2015.00312
PMCID: PMC4637409  PMID: 26617525
antioxidant; DAMP; PAMP; polymorphism; reactive oxygen species; TLR
15.  When to initiate renal replacement therapy: The trend of dialysis initiation 
World Journal of Nephrology  2015;4(5):521-527.
The timing of renal replacement therapy for patients with end-stage renal disease has been subject to considerable variation. The United States Renal Data System shows an ascending trend of early dialysis initiation until 2010, at which point it decreased slightly for the following 2 years. In the 1990s, nephrologists believed that early initiation of dialysis could improve patient survival. Based on the Canadian-United States Peritoneal Dialysis study, the National Kidney Foundation Dialysis Outcomes Quality Initiative recommended that dialysis should be initiated early. Since 2001, several observational studies and 1 randomized controlled trial have found no beneficial effect when patients were placed on dialysis early. In contrast, they found that an increase in mortality was associated with early dialysis initiation. The most recent dialysis initiation guidelines recommend that dialysis should be initiated at an estimated glomerular filtration rate (eGFR) of greater than or equal to 6 mL/min per 1.73 m2. Nevertheless, the decision to start dialysis is mainly based on a predefined eGFR value, and no convincing evidence has demonstrated that patients would benefit from early dialysis initiation as indicated by the eGFR. Even today, the optimal dialysis initiation time remains unknown. The decision of when to start dialysis should be based on careful clinical evaluation.
doi:10.5527/wjn.v4.i5.521
PMCID: PMC4635372  PMID: 26558189
End-stage renal disease; Renal replacement therapy; Dialysis; Estimated glomerular filtration rate; Creatinine clearance; Survival
16.  Redox Roles of Reactive Oxygen Species in Cardiovascular Diseases 
Cardiovascular disease (CVD), a major cause of mortality in the world, has been extensively studied over the past decade. However, the exact mechanism underlying its pathogenesis has not been fully elucidated. Reactive oxygen species (ROS) play a pivotal role in the progression of CVD. Particularly, ROS are commonly engaged in developing typical characteristics of atherosclerosis, one of the dominant CVDs. This review will discuss the involvement of ROS in atherosclerosis, specifically their effect on inflammation, disturbed blood flow and arterial wall remodeling. Pharmacological interventions target ROS in order to alleviate oxidative stress and CVD symptoms, yet results are varied due to the paradoxical role of ROS in CVD. Lack of effectiveness in clinical trials suggests that understanding the exact role of ROS in the pathophysiology of CVD and developing novel treatments, such as antioxidant gene therapy and nanotechnology-related antioxidant delivery, could provide a therapeutic advance in treating CVDs. While genetic therapies focusing on specific antioxidant expression seem promising in CVD treatments, multiple technological challenges exist precluding its immediate clinical applications.
doi:10.3390/ijms161126059
PMCID: PMC4661917  PMID: 26610475
free radical; reactive oxygen species; atherosclerosis; antioxidant
17.  Fine particulate matter in acute exacerbation of COPD 
Chronic obstructive pulmonary disease (COPD) is a common airway disorder. In particular, acute exacerbations of COPD (AECOPD) can significantly reduce pulmonary function. The majority of AECOPD episodes are attributed to infections, although environmental stress also plays a role. Increasing urbanization and associated air pollution, especially in developing countries, have been shown to contribute to COPD pathogenesis. Elevated levels of particulate matter (PM) in polluted air are strongly correlated with the onset and development of various respiratory diseases. In this review, we have conducted an extensive literature search of recent studies of the role of PM2.5 (fine PM) in AECOPD. PM2.5 leads to AECOPD via inflammation, oxidative stress (OS), immune dysfunction, and altered airway epithelial structure and microbiome. Reducing PM2.5 levels is a viable approach to lower AECOPD incidence, attenuate COPD progression and decrease the associated healthcare burden.
doi:10.3389/fphys.2015.00294
PMCID: PMC4617054  PMID: 26557095
AECOPD; PM2.5; oxidative stress; inflammation; alveolar macrophages
18.  The Role of Oxidative Stress-Induced Epigenetic Alterations in Amyloid-β Production in Alzheimer's Disease 
An increasing number of studies have proposed a strong correlation between reactive oxygen species (ROS)-induced oxidative stress (OS) and the pathogenesis of Alzheimer's disease (AD). With over five million people diagnosed in the United States alone, AD is the most common type of dementia worldwide. AD includes progressive neurodegeneration, followed by memory loss and reduced cognitive ability. Characterized by the formation of amyloid-beta (Aβ) plaques as a hallmark, the connection between ROS and AD is compelling. Analyzing the ROS response of essential proteins in the amyloidogenic pathway, such as amyloid-beta precursor protein (APP) and beta-secretase (BACE1), along with influential signaling programs of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and c-Jun N-terminal kinase (JNK), has helped visualize the path between OS and Aβ overproduction. In this review, attention will be paid to significant advances in the area of OS, epigenetics, and their influence on Aβ plaque assembly. Additionally, we aim to discuss available treatment options for AD that include antioxidant supplements, Asian traditional medicines, metal-protein-attenuating compounds, and histone modifying inhibitors.
doi:10.1155/2015/604658
PMCID: PMC4620382  PMID: 26543520
19.  Nitric oxide in cancer metastasis 
Cancer letters  2014;353(1):1-7.
COX-2, cyclooxygenase; CXCR4, CXC chemokine receptor 4; ECM, extracellular matrix; ELAM-1, endothelial leukocyte adhesion molecule 1; eNOS, endothelial nitric oxide synthase; GC, guanylyl cyclase; HIF-1, hypoxia-inducible factor-1; HUVECs, human umbilical vascular endothelial cells; IL-33, cytokine interleukin-33; iNOS, inducible nitric oxide synthase; MAPK, mitogen-activated protein kinase; MMP, matrix metalloproteinase; nNOS, neuronal nitric oxide synthase; NO•, nitric oxide; NO•-NSAIDs, nitric oxide-releasing non-steroidal anti-inflammatory drugs; NOS, nitric oxide synthase; PCNA, proliferating cell nuclear antigen; PKC, protein kinase C; QUER, quercetin; TPA, 12-O-tetradecanoylphorbol 13-acetate; t-PTER, trans-pterostilbene; VEGF-C, vascular endothelial growth factor-C
doi:10.1016/j.canlet.2014.07.014
PMCID: PMC4150837  PMID: 25079686
iNOS; NSAIDs; tumor; signaling; hypoxia
20.  Molecular Characterization of Reactive Oxygen Species in Myocardial Ischemia-Reperfusion Injury 
BioMed Research International  2015;2015:864946.
Myocardial ischemia-reperfusion (I/R) injury is experienced by individuals suffering from cardiovascular diseases such as coronary heart diseases and subsequently undergoing reperfusion treatments in order to manage the conditions. The occlusion of blood flow to the tissue, termed ischemia, can be especially detrimental to the heart due to its high energy demand. Several cellular alterations have been observed upon the onset of ischemia. The danger created by cardiac ischemia is somewhat paradoxical in that a return of blood to the tissue can result in further damage. Reactive oxygen species (ROS) have been studied intensively to reveal their role in myocardial I/R injury. Under normal conditions, ROS function as a mediator in many cell signaling pathways. However, stressful environments significantly induce the generation of ROS which causes the level to exceed body's antioxidant defense system. Such altered redox homeostasis is implicated in myocardial I/R injury. Despite the detrimental effects from ROS, low levels of ROS have been shown to exert a protective effect in the ischemic preconditioning. In this review, we will summarize the detrimental role of ROS in myocardial I/R injury, the protective mechanism induced by ROS, and potential treatments for ROS-related myocardial injury.
doi:10.1155/2015/864946
PMCID: PMC4609796  PMID: 26509170
21.  Investigation on Abnormal Iron Metabolism and Related Inflammation in Parkinson Disease Patients with Probable RBD 
PLoS ONE  2015;10(10):e0138997.
Objective
To investigate potential mechanisms involving abnormal iron metabolism and related inflammation in Parkinson disease (PD) patients with probable rapid eye movement sleep behavior disorder (PRBD).
Methods
Total 210 PD patients and 31 controls were consecutively recruited. PD patients were evaluated by RBD Screening Questionnaire (RBDSQ) and classified into PRBD and probable no RBD (NPRBD) groups. Demographics information were recorded and clinical symptoms were evaluated by series of rating scales. Levels of iron and related proteins and inflammatory factors in cerebrospinal fluid (CSF) and serum were detected. Comparisons among control, NPRBD and PRBD groups and correlation analyses between RBDSQ score and levels of above factors were performed.
Results
(1)The frequency of PRBD in PD patients is 31.90%. (2)PRBD group has longer disease duration, more advanced disease stage, severer motor symptoms and more non-motor symptoms than NPRBD group. (3)In CSF, levels of iron, transferrin, NO and IL–1β in PRBD group are prominently increased. RBDSQ score is positively correlated with the levels of iron, transferrin, NO and IL–1β in PD group. Iron level is positively correlated with the levels of NO and IL–1β in PD group. (4)In serum, transferrin level is prominently decreased in PRBD group. PGE2 level in PRBD group is drastically enhanced. RBDSQ score exhibits a positive correlation with PGE2 level in PD group.
Conclusions
PRBD is common in PD patients. PRBD group has severer motor symptoms and more non-motor symptoms. Excessive iron in brain resulted from abnormal iron metabolism in central and peripheral systems is correlated with PRBD through neuroinflammation.
doi:10.1371/journal.pone.0138997
PMCID: PMC4592206  PMID: 26431210
22.  Moisture Sorption and Thermodynamic Properties of Vacuum-Dried Capsosiphon fulvescens Powder 
The moisture sorption isotherms of vacuum-dried edible green alga (Capsosiphon fulvescens) powders were determined at 25, 35, and 45°C and water activity (aw) in the range of 0.11~0.94. An inversion effect of temperature was found at high water activity (>0.75). Various mathematical models were fitted to the experimental data, and Brunauer, Emmett, and Teller model was found to be the most suitable model describing the relationship between equilibrium moisture content and water activity (<0.45). Henderson model could also provide excellent agreement between the experimental and predicted values despite of the intersection point. Net isosteric heat of adsorption decreased from 15.77 to 9.08 kJ/mol with an increase in equilibrium moisture content from 0.055 to 0.090 kg H2O/kg solids. The isokinetic temperature (Tβ) was 434.79 K, at which all the adsorption reactions took place at the same rate. The enthalpy-entropy compensation suggested that the mechanism of the adsorption process was shown to be enthalpy-driven.
doi:10.3746/pnf.2015.20.3.215
PMCID: PMC4596349  PMID: 26451360
Capsosiphon fulvescens; moisture sorption; thermodynamic properties; vacuum-dried
23.  Two-times weekly hemodialysis in China: frequency, associated patient and treatment characteristics and Quality of Life in the China Dialysis Outcomes and Practice Patterns study 
Nephrology Dialysis Transplantation  2013;29(9):1770-1777.
…Questioning the wisdom of the 30-year old paradigm of thrice-weekly HD treatments is a major challenge. However, we dare to question the wisdom of ‘one HD regimen is good for all’ and propose to examine the role of personalized and incremental HD, ranging from once a week to daily HD…
Background
Renal replacement therapy is rapidly expanding in China, and two-times weekly dialysis is common, but detailed data on practice patterns are currently limited. Using cross-sectional data from the China Dialysis Outcomes and Practice Patterns Study (DOPPS), we describe the hemodialysis practice in China compared with other DOPPS countries, examining demographic, social and clinical characteristics of patients on two-times weekly dialysis.
Methods
The DOPPS protocol was implemented in 2011 among a cross-section of 1379 patients in 45 facilities in Beijing, Guangzhou and Shanghai. Data from China were compared with a cross section of 11 054 patients from the core DOPPS countries (collected 2009–11). Among China DOPPS patients, logistic and linear regression were used to describe the association of dialysis frequency with patient and treatment characteristics and quality of life.
Results
A total of 26% of the patients in China were dialyzing two times weekly, compared with < 5% in other DOPPS regions. Standardized Kt/V was lowest in China (2.01) compared with other regions (2.12–2.27). Female sex, shorter dialysis vintage, lower socioeconomic status, less health insurance coverage, and lack of diabetes and hypertension were associated with dialyzing two times weekly (versus three times weekly). Patients dialyzing two times per week had longer treatment times and lower standardized Kt/V, but similar quality of life scores.
Conclusions
Two-times weekly dialysis is common in China, particularly among patients, who started dialysis more recently, have a lower comorbidity burden and have financial constraints. Quality of life scores do not differ between the two-times and three-times weekly groups. The effect on clinical outcomes merits further study.
doi:10.1093/ndt/gft472
PMCID: PMC4155454  PMID: 24322579
hemodialysis adequacy; hemodialysis frequency; outcomes; practice patterns; quality of life
24.  Effect and Potential Mechanism of Electroacupuncture Add-On Treatment in Patients with Parkinson's Disease 
Objectives. To explore effectiveness and mechanisms of electroacupuncture (EA) add-on treatment in Parkinson's disease (PD) patients. Methods. Fifty PD patients were randomly assigned to drug plus EA (D + EA) group and drug alone (D) group. Subjects in D + EA group received stimulation in points of bilateral fengfu, fengchi, hegu, and central dazhui. Participants were evaluated by scales for motor and nonmotor symptoms. Levels of neuroinflammatory factors and neurotransmitters in serum were detected. Results. EA add-on treatment remarkably reduced scores of Unified Parkinson's Disease Rating Scale (UPDRS) III and its subitems of tremor, rigidity, and bradykinesia and conspicuously decreased UPDRS III scores in patients with bradykinesia-rigidity and mixed types and mild severity. Depression and sleep disturbances were eased, which were reflected by decreased scores of Hamilton Depression Rating Scale, Pittsburgh Sleep Quality Index, and elevated noradrenaline level. Effects of EA add-on treatment on motor symptoms and sleep disturbances were superior to drug alone treatment, markedly improving life quality of PD patients. EA add-on treatment decreased nitric oxide level in serum. Conclusions. EA add-on treatment is effective on most motor symptoms and some nonmotor symptoms and is particularly efficacious in PD patients at early stage. Antineuroinflammation may be a mechanism of EA add-on treatment.
doi:10.1155/2015/692795
PMCID: PMC4550783  PMID: 26351515
25.  Dosimetric Evaluation of Intensity-Modulated Radiotherapy, Volumetric Modulated Arc Therapy, and Helical Tomotherapy for Hippocampal-Avoidance Whole Brain Radiotherapy 
PLoS ONE  2015;10(4):e0126222.
Background
Whole brain radiotherapy (WBRT) is a vital tool in radiation oncology and beyond, but it can result in adverse health effects such as neurocognitive decline. Hippocampal Avoidance WBRT (HA-WBRT) is a strategy that aims to mitigate the neuro-cognitive side effects of whole brain radiotherapy treatment by sparing the hippocampi while delivering the prescribed dose to the rest of the brain. Several competing modalities capable of delivering HA-WBRT, include: Philips Pinnacle step-and-shoot intensity modulated radiotherapy (IMRT), Varian RapidArc volumetric modulated arc therapy (RapidArc), and helical TomoTherapy (TomoTherapy).
Methods
In this study we compared these methods using 10 patient datasets. Anonymized planning CT (computerized tomography) scans and contour data based on fused MRI images were collected. Three independent planners generated treatment plans for the patients using three modalities, respectively. All treatment plans met the RTOG 0933 criteria for HA-WBRT treatment.
Results
In dosimetric comparisons between the three modalities, TomoTherapy has a significantly superior homogeneity index of 0.15 ± 0.03 compared to the other two modalities (0.28 ± .04, p < .005 for IMRT and 0.22 ± 0.03, p < .005 for RapidArc). RapidArc has the fastest average delivery time of 2.5 min compared to the other modalities (15 min for IMRT and 18 min for TomoTherapy).
Conclusion
TomoTherapy is considered to be the preferred modality for HA-WBRT due to its superior dose distribution. When TomoTherapy is not available or treatment time is a concern, RapidArc can provide sufficient dose distribution meeting RTOG criteria and efficient treatment delivery.
doi:10.1371/journal.pone.0126222
PMCID: PMC4404135  PMID: 25894615

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