OBJECTIVEThe changes in serum adipokines and cytokines related to oxidative stress were examined during 3 months 'Off to On' and 'On to Off' periods using negatively charged particle-dominant indoor air conditions (NCPDIAC).

METHODSSeven volunteers participated in the study, which included 'OFF to 3 months ON' periods (ON trials) for a total of 16 times, and 'ON to 3 months OFF' (OFF trials) periods for a total of 13 times.

RESULTSWith the exception of one case, serum amyloid A (SAA) levels decreased significantly during the ON trials.

CONCLUSIONConsidering that SAA is an acute phase reactive protein such as C reactive protein (CRP), this observed decrease might indicate the prevention of cardiovascular and atherosclerotic changes, since an increase in high-sensitive CRP is associated with the subsequent detection of these events.

Adult ; Air ; analysis ; Air Pollution, Indoor ; Environmental Monitoring ; Female ; Housing ; Humans ; Male ; Serum Amyloid A Protein ; metabolism

BACKGROUND/OBJECTIVES: One of the mechanisms considered to be prevalent in the development of Alzheimer's disease (AD) is hyper-stimulation of microglia. Black chokeberry (Aronia melanocapa L.) is widely used to treat diabetes and atherosclerosis, and is known to exert anti-oxidant and anti-inflammatory effects; however, its neuroprotective effects have not been elucidated thus far. MATERIALS/METHODS: We undertook to assess the anti-inflammatory effect of the ethanolic extract of black chokeberry friut (BCE) in BV2 cells, and evaluate its neuroprotective effect in the lipopolysaccharide (LPS)-induced mouse model of AD. RESULTS: Following stimulation of BV2 cells by LPS, exposure to BCE significantly reduced the generation of nitric oxide as well as mRNA levels of numerous inflammatory factors such as inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), interleukin 1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α). In addition, AD was induced in a mouse model by intraperitoneal injection of LPS (250 µg/kg), subsequent to which we investigated the neuroprotective effects of BCE (50 mg/kg) on brain damage. We observed that BCE significantly reduced tissue damage in the hippocampus by downregulating iNOS, COX-2, and TNF-α levels. We further identified the quinic acids in BCE using liquid chromatography-mass spectrometry (LCMS). Furthermore, we confirmed the neuroprotective effect of BCE and quinic acid on amyloid beta-induced cell death in rat hippocampal primary neurons. CONCLUSIONS: Our findings suggest that black chokeberry has protective effects against the development of AD.
Alzheimer Disease ; Amyloid ; Animals ; Atherosclerosis ; Brain ; Cell Death ; Cyclooxygenase 2 ; Ethanol ; Hippocampus ; Inflammation ; Injections, Intraperitoneal ; Interleukin-1beta ; Mice ; Mice, Inbred ICR ; Microglia ; Neurons ; Neuroprotective Agents ; Nitric Oxide ; Nitric Oxide Synthase Type II ; Phytochemicals ; Quinic Acid ; Rats ; RNA, Messenger ; Spectrum Analysis ; Tumor Necrosis Factor-alpha

PURPOSE: The measuring Epstein-Barr virus (EBV) DNA is an important predictor of nasopharyngeal carcinoma (NPC). This study evaluated the predictive value of pretreatment serum amyloid A (SAA) and C-reactive protein (CRP) comparing with EBV DNA in patients with NPC. MATERIALS AND METHODS: In an observational study of 419 non-metastatic NPC patients, we prospectively evaluated the prognostic effects of pretreatment SAA, CRP, and EBV DNA on survival. The primary end-point was progress-free survival (PFS). RESULTS: The median level of SAA and CRP was 4.28 mg/L and 1.88 mg/L, respectively. For the high-SAA group (> 4.28 mg/L) versus the low-SAA (≤ 4.28 mg/L) group and the high-CRP group (> 1.88 mg/L) versus the low-CRP (≤ 1.88 mg/L) group, the 5-year PFS was 64.5% versus 73.1% (p=0.013) and 65.2% versus 73.3% (p=0.064), respectively. EBV DNA detection showed a superior predictive result, the 5-year PFS in the EBV DNA ≥ 1,500 copies/mL group was obviously different than the EBV DNA < 1,500 copies/mL group (62.2% versus 77.8%, p < 0.001). Multifactorial Cox regression analysis confirmed that in the PFS, the independent prognostic factors were including EBV DNA (hazard ratio [HR], 1.788; p=0.009), tumour stage (HR, 1.903; p=0.021), and node stage (HR, 1.498; p=0.049), but the SAA and CRP were not included in the independent prognostic factors. CONCLUSION: The results of SAA and CRP had a certain relationship with the prognosis of NPC, and the prognosis of patients with high level of SAA and CRP were poor. However, the predictive ability of SAA and CRP was lower than that of EBV DNA.
C-Reactive Protein* ; DNA* ; Herpesvirus 4, Human* ; Humans ; Observational Study ; Prognosis ; Prospective Studies* ; Serum Amyloid A Protein* ; Survival Analysis

BACKGROUNDAcne inversa (AI), also called hidradenitis suppurativa, is a chronic, inflammatory, recurrent skin disease of the hair follicle. Familial AI shows autosomal-dominant inheritance caused by mutations in the γ-secretase genes. This study was aimed to identify the specific mutations in the γ-secretase genes in two Chinese families with AI.

METHODSIn this study, two Chinese families with AI were investigated. All the affected individuals in the two families mainly manifested with multiple comedones, pitted scars, and a few inflammatory nodules on their face, neck, trunk, axilla, buttocks, upper arms, and thighs. Reticulate pigmentation in the flexures areas resembled Dowling-Degos disease clinically and pathologically. In addition, one of the affected individuals developed anal canal squamous cell carcinoma. Molecular mutation analysis of γ-secretase genes including PSENEN, PSEN1, and NCSTN was performed by polymerase chain reaction and direct DNA sequencing.

RESULTSTwo novel mutations of PSENEN gene were identified, including a heterozygous missense mutation c.194T>G (p.L65R) and a splice site mutation c.167-2A>G.

CONCLUSIONSThe identification of the two mutations could expand the spectrum of mutations in the γ-secretase genes underlying AI and provide valuable information for further study of genotype-phenotype correlations.

Amyloid Precursor Protein Secretases ; genetics ; DNA Mutational Analysis ; Female ; Hidradenitis Suppurativa ; diagnosis ; genetics ; Humans ; Hyperpigmentation ; diagnosis ; Male ; Membrane Proteins ; genetics ; Middle Aged ; Mutation ; Pedigree ; Skin Abnormalities ; diagnosis ; Skin Diseases, Genetic ; diagnosis ; Skin Diseases, Papulosquamous ; diagnosis

Microglia play a pivotal role in clearance of Aβ by degrading them in lysosomes, countering amyloid plaque pathogenesis in Alzheimer's disease (AD). Recent evidence suggests that lysosomal dysfunction leads to insufficient elimination of toxic protein aggregates. We tested whether enhancing lysosomal function with transcription factor EB (TFEB), an essential regulator modulating lysosomal pathways, would promote Aβ clearance in microglia. Here we show that microglial expression of TFEB facilitates fibrillar Aβ (fAβ) degradation and reduces deposited amyloid plaques, which are further enhanced by deacetylation of TFEB. Using mass spectrometry analysis, we firstly confirmed acetylation as a previously unreported modification of TFEB and found that SIRT1 directly interacted with and deacetylated TFEB at lysine residue 116. Subsequently, SIRT1 overexpression enhanced lysosomal function and fAβ degradation by upregulating transcriptional levels of TFEB downstream targets, which could be inhibited when TFEB was knocked down. Furthermore, overexpression of deacetylated TFEB at K116R mutant in microglia accelerated intracellular fAβ degradation by stimulating lysosomal biogenesis and greatly reduced the deposited amyloid plaques in the brain slices of APP/PS1 transgenic mice. Our findings reveal that deacetylation of TFEB could regulate lysosomal biogenesis and fAβ degradation, making microglial activation of TFEB a possible strategy for attenuating amyloid plaque deposition in AD.
Alzheimer Disease ; metabolism ; pathology ; Amyloid beta-Peptides ; metabolism ; Amyloid beta-Protein Precursor ; genetics ; metabolism ; Animals ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; chemistry ; genetics ; metabolism ; Brain ; metabolism ; Cells, Cultured ; Chloride Channels ; genetics ; metabolism ; Disease Models, Animal ; HEK293 Cells ; Humans ; Lysosomes ; genetics ; metabolism ; Mice ; Mice, Transgenic ; Microglia ; cytology ; metabolism ; Mutagenesis, Site-Directed ; Peptides ; analysis ; chemistry ; Protein Binding ; RNA Interference ; Sirtuin 1 ; antagonists & inhibitors ; genetics ; metabolism

Cranberry extract (CBE) rich in polyphenols are potent to delay paralysis induced by alleviating β-amyloid (Aβ) toxicity in C. elegans model of Alzheimer's disease (AD). In order to better apply CBE as an anti-AD agent efficiently, we sought to deterrmine whether preventive or therapeutic effect contributes more prominently toward CBE's anti-AD activity. As the level of Aβ toxicity and memory health are two major pathological parameters in AD, in the present study, we compared the effects of CBE on Aβ toxicity and memory health in the C. elegans AD model treated with preventive and therapeutic protocols. Our results revealed that CBE prominently showed the preventive efficacy, providing a basis for further investigation of these effects in mammals.
Alzheimer Disease ; drug therapy ; genetics ; metabolism ; psychology ; Amyloid beta-Peptides ; metabolism ; toxicity ; Animals ; Caenorhabditis elegans ; drug effects ; metabolism ; Dietary Supplements ; analysis ; Disease Models, Animal ; Female ; Fruit ; chemistry ; Humans ; Male ; Memory ; drug effects ; Plant Extracts ; administration & dosage ; Vaccinium macrocarpon ; chemistry

BACKGROUNDElevated levels of serum C-reactive protein (CRP) have been reported to have prognostic significance in lung cancer patients. This study aimed to further identify CRP-bound components as prognostic markers for lung cancer and validate their prognostic value.

METHODSCRP-bound components obtained from the serum samples from lung cancer patients or healthy controls were analyzed by differential proteomics analysis. CRP-bound serum amyloid A (CRP-SAA) was evaluated by co-immunoprecipitation (IP). Serum samples from two independent cohorts with lung cancer (retrospective cohort, 242 patients; prospective cohort, 222 patients) and healthy controls (159 subjects) were used to evaluate the prognostic value of CRP-SAA by enzyme-linked immunosorbent assay.

RESULTSCRP-SAA was identified specifically in serum samples from lung cancer patients by proteomic analysis. CRP binding to SAA was confirmed by co-IP in serum samples from lung cancer patients and cell culture media. The level of CRP-SAA was significantly higher in patients than in healthy controls (0.37 ± 0.58 vs. 0.03 ± 0.04, P < 0.001). Elevated CRP-SAA levels were significantly associated with severe clinical features of lung cancer. The elevation of CRP-SAA was associated with lower survival rates for both the retrospective (hazard ration [HR] = 2.181, 95% confidence interval [CI] = 1.641-2.897, P < 0.001) and the prospective cohorts (HR = 2.744, 95% CI = 1.810-4.161, P < 0.001). Multivariate Cox analysis showed that CRP-SAA was an independent prognostic marker for lung cancer. Remarkably, in stages I-II patients, only CRP-SAA, not total SAA or CRP, showed significant association with overall survival in two cohorts. Moreover, univariate and multivariate Cox analyses also showed that only CRP-SAA could be used as an independent prognostic marker for early-stage lung cancer patients.

CONCLUSIONCRP-SAA could be a better prognostic marker for lung cancer than total SAA or CRP, especially in early-stage patients.

Biomarkers ; C-Reactive Protein ; Enzyme-Linked Immunosorbent Assay ; Humans ; Lung Neoplasms ; Multivariate Analysis ; Prognosis ; Prospective Studies ; Proteomics ; Retrospective Studies ; Serum Amyloid A Protein

BACKGROUNDEarly diagnosis assumes a vital role in an effective treatment of Alzheimer's disease (AD). Most of the current studies can only make an AD diagnosis after the manifestation of typical clinical symptoms. The present study aimed to investigate typical and other biomarkers of AD to find a possible early biomarker.

METHODSA total of 14 5XFAD mice (at 3 and 6 months old), with 14 age-matched wild-type (WT) mice as control, were enrolled in this case-control study. Morris water maze test was performed to evaluate the cognitive function; buried food pellet test and olfactory maze test were employed to investigate the olfactory function; immunofluorescence to detect amyloid deposition and positron emission tomography to examine 2-deoxy-2-(18F) fluoro-D-glucose ([18F]-FDG) uptake in the hippocampus and cerebral cortex.

RESULTSWith the increasing age, cognitive performance (P = 0.0262) and olfactory function were significantly deteriorated (day 1 P = 0.0012, day 2 P = 0.0031, day 3 P = 0.0160, respectively) and the (18F)-FDG uptake was markedly decreased in multi-cerebral regions including the olfactory bulb (P < 0.0001), hippocampus (P = 0.0121), and cerebral cortex (P < 0.0001). Of note, in 3-month-old 5XFAD mice, a significant decline of (18F)-FDG uptake in the olfactory bulb was found when compared with that of age-matched WT mice (P = 0.023) while no significant difference was present when the uptakes in other cerebral regions were compared.

CONCLUSIONSThe decline of (18F)-FDG uptake in the olfactory bulb occurs earlier than other incidents, serving as an earlier in vivo biological marker of AD in 5XFAD mice and making early diagnosis of AD possibly.

Alzheimer Disease ; diagnosis ; Amyloid ; analysis ; Animals ; Animals, Genetically Modified ; Biomarkers ; analysis ; Fluorodeoxyglucose F18 ; metabolism ; Glucose ; metabolism ; Mice ; Olfactory Bulb ; metabolism ; Positron-Emission Tomography

OBJECTIVETo study the value of Pentraxin 3 (PTX3) in diagnosing the severity and cardiovascular function of the critically ill children. Method A total of 178 patients who were older than 28 days, with acute infection of respiratory or neurological system, excluding chronic or special disease, and admitted to the pediatric intensive care unit (PICU) of Hunan Children's Hospital from October 1, 2013 to April 30, 2014 were enrolled, including 102 male cases and 76 female cases. The ages ranged from 1 month to 13 years and 1 month, 78 of them were less than 1 year old ; 58 cases were between 1 to 3 years old; 42 cases were above 3 years old; 101 cases were diagnosed as respiratory system diseases, 77 cases had nervous system diseases. PTX3 was detected with enzyme-linked immunosorbent assay (ELISA) within 1 d after enrollment, at 3 days and 7 days, meanwhile, troponin, myocardial enzyme, brain-type natriuretic peptide (BNP), C-reactive protein (CRP), plasma calcitonin (PCT) and WBC etc. Were measured. According to the plasma PTX3 value which were measured within 24 h after enrollment the patients were divided into three groups: mildly elevated group (< 44 µg/L) 41 cases; moderately elevated group (44 - < 132 µg/L) in 66 cases; severely elevated group 71 cases (132 µg/L or higher). Those 178 patients were divided into 3 groups according to the degree of infection: non-sepsis group (78 cases), sepsis group (70 cases), severe sepsis group (30 cases), and in each group, those with heart failure were respectively 19 cases, 28 cases, 17 cases. Analysis of the plasma PTX3 expression changes in different clinical manifestations, different condition, different degrees of organ damages and prognosis for the patient. The continuous variables were analyzed with t-test, F-test, H-test, the categorical variables were analyzed with Chi-square test, and the correlation analysis was performed to calculate Pearson coefficients.

RESULTThe PTX3 value measured within 24 h after enrollment increased with the degree of infection (50. 4(35. 2,70. 4) µg/L; 175. 8 (99. 6, 309. 9) µg/L;419. 9 (168. 3, 468. 6) µg/L; H = 88. 345, P = 0. 000). PTX3 level gradually declined, while in severe sepsis group decreased slowly (P <0. 05); the area under the ROC curve of Plasma PTX3 was larger than that of other inflammatory markers such as CRP and PCT, white blood cells and neutrophils in the diagnosis of sepsis; while the former three are PTX3, PCT and CRP (the sensitivity and specificity respectively were 0. 77, 0. 68; 0. 66, 0. 6; 0. 47, 0. 55); the PTX3 value of the severely elevated group was significantly higher than those of the mildly and moderately elevated groups (P <0. 05). The proportion of having 3 or more organs failure increased as the PTX3 rising among the groups of mildly elevated group, moderately elevated group and severely elevated group (1(2. 4%), 4(6. 1%), 14(19. 7%) χ2 =16. 16,P = 0. 000); and in each group, the proportion of having good and poor prognosis for these three groups were different (33 (80.5%) and 8 (19. 5%), 35 (53%) and 31 (47%), 28 (39.4%) and 43 (60.6%), χ = 17. 663, P = 0. 000). The K-M curve for these three groups had statistically significant difference (χ2 = 7. 086, P = 0. 029). Those with heart failure had higher PTX3 value than those in non-heart failure at the same degree of infection. PTX3 value increased with myocardial enzyme (troponin, creatine kinase isoenzyme, BNP) levels. In the diagnosis of heart failure, the area under the ROC curve were respectively PTX3 0. 824; BNP 0. 772; CM-KB 0. 643; CNTIO. 671, the sensitivity and specificity were PTX3 0. 8, 0. 58; CK-MB 0. 56,0. 79; CTNI 0. 60,0. 69; BNP 0. 73, 0. 58. In terms of predicting the prognosis of sepsis with heart failure complications, the PTX3 value's area under ROC curve was larger than that of BNP (respectively 0. 844, 0. 472).

CONCLUSIONThe PTX3 is an objective biochemical marker in diagnosis of sepsis; it is helpful in assessment of severity and prognosis of sepsis; it also has a certain clinical value in the assessment of sepsis cardiovascular function damage.

Adolescent ; Biomarkers ; blood ; C-Reactive Protein ; analysis ; Calcitonin ; blood ; Cardiovascular System ; physiopathology ; Child ; Child, Preschool ; Creatine Kinase ; blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Infant ; Intensive Care Units, Pediatric ; Leukocyte Count ; Male ; Natriuretic Peptide, Brain ; blood ; Prognosis ; Protein Precursors ; blood ; ROC Curve ; Sensitivity and Specificity ; Sepsis ; diagnosis ; physiopathology ; Serum Amyloid P-Component ; analysis ; Troponin ; blood

OBJECTIVETo screen biomarkers which can be used as an auxiliary method in the diagnosis of Henoch-Schönlein purpura (HSP) and to evaluate their diagnostic values by receiver operating characteristic (ROC) curve analysis.

METHODSA total of 127 children diagnosed with HSP between April 2012 and March 2014 were included in the HSP group and an equal number of healthy children were included in the control group. Twelve parameters, i.e., serum amyloid protein A (SAA), interleukin-6 (IL-6), immunoglobulins (IgA, IgG, IgM, and IgE), C-reactive protein (CRP), white blood cell (WBC) count, complements C3 and C4, anti-streptolysin O, and ferritin, were analyzed. The values of the screened biomarkers for diagnosis of HSP were assessed by ROC curve analysis.

RESULTSThe HSP group had significantly higher levels of SAA, IL-6, CRP, WBC, IgA, and IgM than the control group (P<0.05). The areas under the ROC curve of SAA, IL-6, WBC, IgA, and IgM for the diagnosis of HSP were higher than 0.7 (P<0.05). The optimal cut-off values of SAA, IgA, IgM, WBC, and IL-6 for the diagnosis of HSP were 3.035 μg/mL, 1579.5 mg/L, 922.5 mg/L, 8.850 × 10⁹/L, and 7.035 pg/mL, respectively; the corresponding sensitivities of the optimal cut-off values for the diagnosis of HSP were 95.1%, 75.6%, 72.3%, 78.0%, and 63.4%, respectively, and the corresponding specificities were 90.2%, 85.4%, 82.4%, 70.7%, and 80.5%, respectively.

CONCLUSIONSSAA, IgA, IgM, WBC, and IL-6 are valuable biomarkers for clinical diagnosis of HSP and among them SAA seems to be the best one.

Adolescent ; Biomarkers ; blood ; C-Reactive Protein ; analysis ; Child ; Child, Preschool ; Female ; Humans ; Male ; Purpura, Schoenlein-Henoch ; blood ; diagnosis ; ROC Curve ; Serum Amyloid A Protein ; analysis