879982

Serum miR-146a, miR-155 and miR-210 as potential markers of Graves disease

Lei Zheng a, b , Chunbo Zhuang a, b , Xiaobei Wang b, * , Liang Ming a, *

a

Department of Clinical Laboratory Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Jian She East Road, Zhengzhou, Henan, P. R. China.

b

Department of Clinical Laboratory Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1227 Jie Fang Road, Wuhan, Hubei, P. R. China

*

Corresponding author. Liang Ming, email: mingliang0372@163.com, Tel: +86037166913118; Fax: +86037166913118. Xiaobei Wang, email: windflower6174@gmail.com, Tel: +8602785726310; Fax: +8602785726310.

Treg-associated circulating miRNAs in Graves' disease

Abstract

Background: Previous studies have demonstrated that dysfunctional regulatory T cells (Tregs) may be associated with Graves disease (GD). In this study, we evaluated four serum Treg-associated miRNAs (miR-210, miR-182, miR-155 and miR-146a) expressions and assessed the potential of serum miRNAs as biomarkers of GD. Methods: Foxp3 and serum miRNAs expressions both in GD patients and healthy controls were measured by RT-PCR. Results: Serum miR-210 in GD patients was significantly higher than healthy controls (2.64-fold, P0.055%

250

1

2

3

4

5

6

7

8

246

247

248

249

250

(X

cv

6.7

5.2

4.8

8.1

5.0

5.1

4.2

5.9

4.6

4.9

5.9

6.2

7.1

5.1

2.5

6.4

5.0

4.9

7.9

4.6

5.2

4.0

5.8

4.5

4.9

5.8

6.1

7.3

4.9

2.4

%

4.6

4

2.0

2.5

2.5

1.9

5.0

1.7

2.0

0

1.7

1.6

2.7

4.0

4

3 H9

4

[6]HBA1C4HBA1CLPLCHBA1C[8]HBA1C[3-4]HPLC4500 [5]HPLCAHPLC [6]EDTA-K2HbA1c2-8 []HbA1c[8]11HbA1cHbA1c[9][10]

[1] [J] 201037(19)p3719-3720

[2] [J]20141240p55-56

[3] [J] 201661313 p1839-1840

[4] [J] 20129918p967-968

[5] [J] 201553610p1458-1459

[6] [J] 275200910p465-466

[] [J]2p967-968

[8] [J]2009299p805-807

[9] [J] 2012396p714-716

[10] [J] 20133 243p224-225

872133

The reference intervals for HE4, CA125 and ROMA in healthy female

Objectives: HE4 is a tumor marker in diagnosing ovarian cancer. Together with CA125 and ROMA score, it can improve sensitivity and specificity. There are no reports about the serum HE4 reference intervals (RIs) with electrochemiluminescence immunoassay (ECLIA). The RI of ROMA hasnt been established yet. In this study, we establish the RIs for serum HE4, CA125 and ROMA in healthy Chinese female with ECLIA.Methods: Serum HE4 and CA125 concentrations in healthy female were simultaneous measured with ECLIA on Roche Cobas E601 system. The RIs were determined following CLSI C28-A3 guidelines using a nonparametric method.Results: The upper limits of the 95% percentile intervals were 82.62pmol/L for HE4, 30.91 U/ml for CA125 and 19.27 for ROMA. The reference limits for HE4, CA125 and ROMA were 65.87pmol/L, 32.23 U/ml, 13.14 for premenopausal women, and 90.76pmol/L, 27.52 U/ml, 25.46 for postmenopausal women respectively.Conclusion: We established the RIs for serum HE4, CA125 and ROMA with ECLIA in healthy Chinese female. It provided a reference for clinical and laboratory studies.

875749

450052

MethylenetetrahydrofolatereductaseMTHFRtotalhomocysteinetHcyfolateB6VitaminB6,VitB6B12VitaminB12,VitB12age-related cataract,ARC127ARC129tHcyenzyme-linked immuno sorbent assay,ELISAMTHFRVitB6VitB12ROCARC1ARCMTHFRP0.05tHcyP0.052ROCMTHFRtHcy5ARCAUC0.689,0.689,0.732ARCAUC0.8250.8050.855ARCAUC0.7060.7420.8115ARCMTHFRtHcyARC

ROCB6B12MTHFRtHcy

Diagnosis value of plasma indexes of homocystine metabolism for ARC and its subtypes

Abstract: Objective To investigate the diagnostic accuracy of homocystine(Hcy) metabolismindexes, such as MTHFR enzyme activity, total homocystine (tHcy), folic acid (FA), vitaminB6 and Vitamin B12 in age-related cataract (ARC) and its subtypes. Methods In 127 ARC patients and 129 controls, the plasma tHcy levels were detected by an automated assay, while concentrations of MTHFR, folate, vitamin B6, B12 were measured by ELISA. The diagnostic accuracy of each index and combined indexes was assessed by area under the receiver operating characteristics (ROC) curves (AUCs). Results (1) Plasma concentrations of MTHFR activity and FA were significantly lower, while tHcy levels were significantly higher in ARC patients than those in the control group (P0.05). (2)The area under ROC curves (AUC) of MTHFR, tHcy, and combined five indexes above were 0.689, 0.689, 0.732 for the diagnosis of ARC; 0.825, 0.805, 0.855 for the diagnosis of cortical ARC; 0.706, 0.742, 0.811 for the diagnosis of posterior subcapsular ARC. Conclusion: The combination of five indexes could improve the diagnosis efficiency of ARC, whilethe MTHFR activity and tHcy levels could be useful diagnostic markers for cortical ARC and posterior subcapsular ARC,

Key words: age-related cataract, ROC curve, folate, Hcy, MTHFR, vitamin B6, vitamin B12

Age-related cataract, ARC16001[]reactive oxygen speciesROSARC2[]totalhomocysteinetHcyROStHcy ADDIN EN.CITE

[3]MethylenetetrahydrofolatereductaseMTHFRB6VitaminB6,VitB6B12VitaminB12,VitB12tHcyHcyMTHFRtHcyVitB6VitB12ARCARC

1

1.1 20141020154127ARC12915020/40ARCLens opacities classification system LocsARCLocs4Locs2Locs2ARC ADDIN EN.CITE

[4]

1

N

129

6046.5

6953.5

68.54.9

58-86

ARC

127

5442.5

7357.5

68.79.1

52-84

43

1330.2

3069.8

69.79.5

50-84

32

1959.3

1340.7

67.68.8

51-82

23

1043.5

1356.5

67.68.3

56-84

29

1241.4

1758.6

69.39.7

51-84

1.2 EDTA2000g512000r/min10-807020tHcyELISAMTHFRVitB6VitB12ELISA

2

SPSS17.0Graphpad 6.0tP0.051-ROCAUCP95%95%CI=0.05

3

3.1ARCMTHFRtHcyP0.05VitB6VitB12ARCP0.05ARCMTHFRtHcyARCARCP0.054P0.05VitB12ARCVitB12P0.052.

2ARC5

ARC

Mean SD

Mean SD

Mean SD

Mean SD

Mean SD

Mean SD

MTHFRU/L

370.0 51.0

337.6 35.7*

312.8 27.6*

356.8 28.0

334.5 32.5*

355.9 34.1

nmol/L

16.2 1.7

15.0 2.7*

15.4 2.4*

14.5 2.1*

15.0 3.5*

15.0 3.1*

tHcymol/L

10.8 1.9

12.3 2.5*

13.4 2.6*

11.5 2.4

12.4 1.8*

11.6 2.4

VitaminB12pmol/L

271.4 37.7

267.4 30.9

273.0 28.2

265.5 26.1

254.2 38.9*

271.7 30.5

VitaminB6nmol/L

41.6 5.1

41.4 5.2

41.9 5.5

40.8 5.0

39.8 5.7

42.6 4.9

*P0.05

3.2 ARCROC

MTHFRtHcyVitB6VitB12ROC195% CIP%%3MTHFRtHcyVitB6VitB12ROCAUC0.6890.6890.546,0.5120.521MTHFRtHcyVitB6389.82U/L12.67mol/L13.21nmol/L44.70nmol/L300.56pmol/L92.1%39.5%48.4%81.4%23.6%97.7%76.4%31.0%84.3%26.4%MTHFRARCARC

ARCMTHFRtHcyARCARCARCVitB6VitB12ARC

3.3 5ARC

ROC1ARCARCARCAUC0.7320.8550.81180.3%81.4%78.3%72.1%77.5%74.6%ARC

1MTHFRtHcy5ROC

AMTHFRtHcy5ARCROCBMTHFRtHcy5ARCROCCMTHFRtHcy5ARCROC

3:ARC

ARC

ARC

ARC

AUC(95%CI)

%

%

AUC(95%CI)

%

%

AUC(95%CI)

%

%

MTHFR

0.689(0.624-0.754)

92.1

39.5

0.825(0.764-0.887)

93.0

62.8

0.706(0.609-0.803)

91.3

47.3

tHcy

0.689(0.624-0.754)

48.8

81.4

0.805(0.719-0.891)

72.1

81.4

0.742(0.644-0.840)

87.0

62.8

FA

0.546(0.472-0.619)

23.6

97.7

0.502(0.388-0.615)

32.6

82.9

0.656(0.500-0.813)

60.9

76.0

VitB6

0.512(0.441-0.583)

76.4

31.0

0.509(0.408-0.611)

11.6

96.9

0.596(0.471-0.720)

91.3

31.0

VitB12

0.521(0.450-0.593)

84.3

26.4

0.525(0.435-0.616)

88.4

26.4

0.613(0.488-0.738)

56.5

65.9

MTHFR+tHcy+FA+VitB6+VitB12

0.732(0.671-0.793)

80.3

72.1

0.855(0.797-0.913)

81.4

77.5

0.811(0.719-0.902)

78.3

74.6

4

MTHFRtHcyVitB6VitB12ROCARC5ARCMTHFRtHcyARCARC

tHcyROSARC ADDIN EN.CITE

[5]TantHcyARC ADDIN EN.CITE

[3]ROCtHcyARCARCARCtHcyROSARC ADDIN EN.CITE

[6]tHcyARCMTHFRtHcytHcytHcy ADDIN EN.CITE

[7]ARCMTHFRP0.05ROCMTHFRARCARC

VitB6VitB12tHcytHcy8[]1ARC24% ADDIN EN.CITE

[3]ARCtHcyP0.05ROCARC97.7%ARCBARC ADDIN EN.CITE

[9]metaARC ADDIN EN.CITE

[10]ARC VitB12P0.05ROCVitB6VitB12ARC

ARC5ARCARCARCARCARC

[1]PASCOLINI D, MARIOTTI S P. Global estimates of visual impairment: 2010 [J]. The British journal of ophthalmology, 2012, 96(5): 614-8.

[2]BERTHOUD V M, BEYER E C. Oxidative stress, lens gap junctions, and cataracts [J]. Antioxidants & redox signaling, 2009, 11(2): 339-53.

[3]TAN A G, MITCHELL P, ROCHTCHINA E, et al. Serum homocysteine, vitamin B12, and folate, and the prevalence and incidence of posterior subcapsular cataract [J]. Investigative ophthalmology & visual science, 2015, 56(1): 216-20.

[4]CHYLACK L T, JR., WOLFE J K, SINGER D M, et al. The Lens Opacities Classification System III. The Longitudinal Study of Cataract Study Group [J]. Archives of ophthalmology (Chicago, Ill : 1960), 1993, 111(6): 831-6.

[5]ELANCHEZHIAN R, PALSAMY P, MADSON C J, et al. Age-related cataracts: homocysteine coupled endoplasmic reticulum stress and suppression of Nrf2-dependent antioxidant protection [J]. Chemico-biological interactions, 2012, 200(1): 1-10.

[6]IKESUGI K, YAMAMOTO R, MULHERN M L, et al. Role of the unfolded protein response (UPR) in cataract formation [J]. Experimental eye research, 2006, 83(3): 508-16.

[7]QIN X, LI Y, YUAN H, et al. Relationship of MTHFR gene 677C --> T polymorphism, homocysteine, and estimated glomerular filtration rate levels with the risk of new-onset diabetes [J]. Medicine, 2015, 94(7): e563.

[8]ZHANG S, SHI C, MAO C, et al. Plasma Homocysteine, Vitamin B12 and Folate Levels in Multiple System Atrophy: A Case-Control Study [J]. PloS one, 2015, 10(8): e0136468.

[9]GLASER T S, DOSS L E, SHIH G, et al. The Association of Dietary Lutein plus Zeaxanthin and B Vitamins with Cataracts in the Age-Related Eye Disease Study: AREDS Report No. 37 [J]. Ophthalmology, 2015, 122(7): 1471-9.

[10]ZHAO L Q, LI L M, ZHU H, et al. The effect of multivitamin/mineral supplements on age-related cataracts: a systematic review and meta-analysis [J]. Nutrients, 2014, 6(3): 931-49.

876484

PCAFEZH2

EZH2H327H3K27EZH2PRC2EEDSUZ12RbAp46/48EZH2XEZH2EZH2EZH2EZH2 487CDK1EZH2EZH2O--N-EZH2EZH2EZH2Western blotCo-IPReal-time PCRChIPTranswell/EZH2EZH2EZH2PCAFSIRT1PCAFEZH2EZH2K348K348EZH2 345487EZH2PRC2K348EZH2EZH2 K348EZH2EZH2EZH2

882369

graphitic carbon nitrideg-C3N4ATetrabromobisphenolAg-C3N4 g-C3N4 XXEISN-TBBPA g-C3N4g-C3N4-g-C3N4g-C3N4TBBPA0.02 M - 1 M5 nM g-C3N4TBBPAg-C3N4g-C3N4A

882666

455000

::3840:M78.9%MMIgG2257.89%IgA718.42%IgM615.79%37.89%MMP