1.Effect of Hydroxychloroquine Treatment on Dry Eyes in Subjects with Primary Sjögren's Syndrome: a Double-Blind Randomized Control Study.
Chang Ho YOON ; Hyun Ju LEE ; Eun Young LEE ; Eun Bong LEE ; Won Woo LEE ; Mee Kum KIM ; Won Ryang WEE
Journal of Korean Medical Science 2016;31(7):1127-1135
The effect of hydroxychloroquine (HCQ) on dry eye has not been fully determined. This study aimed to compare the 12-week efficacy of HCQ medication with that of a placebo in the management of dry eye in primary Sjögren's syndrome (pSS). A double-blind, randomized control study was conducted in 39 pSS subjects from May 2011 through August 2013. pSS was diagnosed based on the classification criteria of the American-European Consensus Group. Subjects received 300 mg of HCQ or placebo once daily for 12 weeks and were evaluated at baseline, 6, and 12 weeks, with a re-visit at 16 weeks after drug discontinuance. The fluorescein staining score, Schirmer test score, tear film break-up time (TBUT), and ocular surface disease index (OSDI) were measured, and tears and blood were collected for ESR, IL-6, IL-17, B-cell activating factor (BAFF), and Th17 cell analysis. Color testing was performed and the fundus was examined to monitor HCQ complications. Twenty-six subjects completed the follow-up. The fluorescein staining score and Schirmer test score did not differ significantly. The OSDI improved with medication in the HCQ group but was not significantly different between the groups. TBUT, serum IL-6, ESR, serum and tear BAFF, and the proportion of Th17 cells did not change in either group. HCQ at 300 mg daily for 12 weeks has no apparent clinical benefit for dry eye and systemic inflammation in pSS (ClinicalTrials.gov. NCT01601028).
Aged
;
B-Cell Activating Factor/analysis/blood
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Blood Sedimentation
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Double-Blind Method
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Drug Administration Schedule
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Dry Eye Syndromes/complications/*drug therapy
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Enzyme-Linked Immunosorbent Assay
;
Female
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Humans
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Hydroxychloroquine/*therapeutic use
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Interleukin-16/analysis/blood
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Interleukin-17/analysis/blood
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Male
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Middle Aged
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Placebo Effect
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Prospective Studies
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Sjogren's Syndrome/*complications/diagnosis
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Th17 Cells/cytology/immunology
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Treatment Outcome
2.The discriminant analysis of the silicosis's induction on cytokines in phlegm and combined multi-markers.
Yiguang YU ; Rui WANG ; Zhifeng PAN ; Haipeng ZHANG ; Wei ZHANG ; Hui WANG ; Feifei YANG ; Haidong ZHANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2015;33(5):332-336
OBJECTIVETo investigate the changes of cytokines in induced sputum at different stages of silicosis patients.
METHODSA total of 200 workers from one of the Shandong Province gold mine were chosen as object of observation. Among which 40 patients at silicosis stage I and 40 patients at silicosis stage II were divided into silicosis observed object group, silicosis stage I group, silicosis stage II group, and another 80 workers exposed to silica dust without suffering from silicotic Clinical symptoms, however, were chosen as group of dust exposed, and 40 logistical workers without being exposed and history of silicosis's illness were chosen as control group. And ask their basic information by questionnaire. Then, spray-inhalation the induced sputum and apply the ELISA to assess the level of tumor necrosis factor (TNF), interleukin (IL), macrophage inflammatory protein-1 (MIP-1α), monocyte chemotactic factor-1 (MCP-1), metalloproteinases (MMP), transforming growth factor-β (TGF-β), platelet derived growth factor (PDGF) in induced sputum from subjects.
RESULTSThe level of TGF-β [(901.60 ± 30.09) ng/L] in the induced sputumof patients in silicosis stage I group is lower than that in the observed object group [(913.02 ± 20.51) ng/L], and the level of MMP-9 [(212.49 ± 5.97) ng/L], MCP-1 [(129.91 ± 4.30) ng/L] has various degrees of increase than that in control group, observed object group and dust exposed group. All the differences have statistical significances (P < 0.05). The level of TNF-α [(85.76 ± 3.78) ng/L] in the induced sputum of patients in silicosis stage I group reaches the maximum, there are significant differences comparing with that level in the silica dust exposure group and the control group, whose differences are statistically significant (P < 0.05). Compared with the control group, the level of MMP-2 (427.95 ± 23.64) in the induced sputum of patients in silicosis stage I group has increased, whose differences also have statically significant (P < 0.05). Compared with the control group, silica dust exposed group, the observation group of objects, the pneumosilicosis patients of IL-16 in induced sputum IL-16 (21.40 ± 9.24) decreased, the content of PDGF [(5.96 ± 0.51) ng/L], MMP-2 [(447.86 ± 27.10) ng/L], MMP-9 [(223.91 ± 12.28) ng/L], MCP-1 [(122.87 ± 6.08) ng/L] increased, the differences are statistically significant (P < 0.05).
CONCLUSIONAs silicosis biomarkers, TNF-alpha, TGF-beta, IL-16, PDGF, MMP-2, MMP-9 and MCP-1 have certain significance, further suggesting that early detection rate of patients with silicosis can be improved by employing the multiple indexes discriminate equation.
Biomarkers ; metabolism ; Case-Control Studies ; Chemokine CCL2 ; metabolism ; Chemokine CCL3 ; metabolism ; Cytokines ; metabolism ; Discriminant Analysis ; Dust ; Humans ; Interleukin-16 ; metabolism ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Platelet-Derived Growth Factor ; metabolism ; Silicosis ; diagnosis ; Sputum ; chemistry ; Transforming Growth Factor beta ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism
3.Observation of the inflammatory factors level and the correlation between induced sputum and whole lung lavage fluid for silicosis.
Wei ZHANG ; Rui WANG ; Haidong ZHANG ; Yiguang YU ; Hui WANG ; Xiaobao ZHOU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2015;33(3):201-203
OBJECTIVETo detect the inflammatory factors of induced sputum (IS) and whole lung lavage fluid in pneumonoconiosis patients and to explore the correlation between the inflammatory factors with pulmonary function.
METHODSThe records of 45 cases of pneumonoconiosis patients were observed. All patients underwent lung function examination, sputum induction and massive whole lung lavage (WLL) sequentially through advance. IS and whole lung lavage fluid were collected respectively. Inflammatory factors of the two specimens were detected by using enzyme linked immunosorbent assay. The correlation of inflammatory factors between the two specimens was analyzed. The relationship between the inflammatory factor and lung function index was observed. The statistical analysis is performed with SPSS 17.0 for Windows. P < 0.05 is considered to be statistically significant.
RESULTSCytokines (MCP-1, TNF-α MIP-1α, NO(2)(-)/NO(3)(-) and IL-16) were significantly associated between IS and whole lung lavage fluid (P < 0.05), while TNF-α, MCP-1, NO(2)(-)/NO(3)(-) and IL-16 were no significantly associated with lung function index (P > 0.05). MIP-1α was significantly associated with FEV(1.0)/VCmax and MEF(25), respectively (P < 0.05).
CONCLUSIONSInflammatory factors were significantly associated between IS and whole lung lavage fluid, which could indicate early lung injury in pneumonoconiosis patients.
Bronchoalveolar Lavage Fluid ; chemistry ; Chemokine CCL2 ; Chemokine CCL3 ; Cytokines ; analysis ; Humans ; Interleukin-16 ; Lung ; Respiratory Function Tests ; Silicosis ; Sputum ; chemistry ; Tumor Necrosis Factor-alpha
5.Analysis of the level and significance of IL-16 and IL-17 in nasal secretion and in serum of patients with allergic rhinitis and non-allergic rhinitis.
Jianliang CAI ; Shuxiong GUAN ; Zhousheng MAI ; Shifu ZHANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2014;28(11):821-823
OBJECTIVE:
To test the immunoglobulin free light chain (FLC) from nasal secretion and serum of patients with allergic rhinitis(AR)and non-allergic rhinitis(NAR) for the purpose of exploring the possible immunological mechanism.
METHOD:
Ninety consecutive patients were selected between January 2009 and January 2012, involving 45 patients with AR and 45 patients with NAR diagnosed by symptoms,signs,skin prick tests(SPT) and specific IgE (slgE). Forty-five volunteers were chosen as healthy control (HC). According to the visual analogue scale (VAS) scores,the nasal symptoms of AR and NAR,including sneeze. Nasal discharge. Nasal obstruction and nasal itching were compared. ELISA was used to detect the total IgE, IL-16, IL-17 in nasalsecretion and serum. The data was analyzed by SPSS 17.0 software.
RESULT:
There was no statistical difference between AR and NAR group in nasal symptoms (P > 0.05); In serum, IL-16 and IL-17 increased in AR group comparared to NAR group (P < 0.05); IL-16 and IL-17 increased in NAR group comparared to HC group (all P < 0.05); In nasal secretion, IL-16 and IL-17 increased in NAR and AR group comparared to HC group (all P < 0.05).
CONCLUSION
IL-16, IL-17 takes part in the path of physiological process of AR and NAR with the immunological mechanism.
Adolescent
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Adult
;
Case-Control Studies
;
Female
;
Humans
;
Interleukin-16
;
blood
;
metabolism
;
Interleukin-17
;
blood
;
metabolism
;
Male
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Middle Aged
;
Rhinitis
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immunology
;
metabolism
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Rhinitis, Allergic
;
immunology
;
metabolism
;
Young Adult
6.Changes of cell factor in bronchoalveolar lavage fluid in rats exposed to silica.
Wei ZHANG ; Rui WANG ; Xin WANG ; Xiao-bao ZHOU ; Hui WANG ; Hai-dong ZHANG ; Zheng-liang LIU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2013;31(11):801-805
OBJECTIVETo investigate the changes in the levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) in rats exposed to silica dust.
METHODSExperimental rats were randomly divided into control group and three experimental groups (doses of dust: 15, 30, and 60 mg/ml), with 42 rats in each group. Each rat in the control group was treated with 1 ml of normal saline by intratracheal instillation, while each rat in the experimental groups was exposed to 1 ml of silica suspension by a single intratracheal instillation. Seven rats in each group were killed at 1, 3, 7, 14, 21, and 28 days after exposure, and then BALF was collected. Enzyme-linked immunosorbent assay was used to measure the levels of interleukin (IL)-1, IL-6, IL-16, macrophage inflammatory protein-1 alpha (MIP-1α), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β).
RESULTSThe levels of cytokines in each experimental group were higher than those in the control group at any time point. In the early stage of exposure (day 1-3), BALF IL-1 level increased significantly with the increase in dust dose, and on day 14, BALF IL-6 and IL-16 levels increased significantly with the increase in dust dose; the levels of IL-1, IL-6, and IL-16 in the experimental groups reached the peak on day 14. There were significant differences in the levels of MIP-1α and MCP-1 between the experimental groups (FMIP-1α = 30.106, P<0.01; FMCP-1 = 17.193, P<0.01). In each group, the level of MCP-1 varied significantly at different time points (F = 0.618, P>0.05). On day 1-14, BALF TNF-α level increased with the increase in dust dose, with a significant dose-response relationship (P < 0.05). In each experimental group, TNF-α level reached the peak on day 14. On days 14, 21, and 28, the high-dose group had significantly higher BALF TGF-β levels than the low-dose group (P<0.05); on days 14 and 28, the high-dose group had significantly higher BALF TGF-β levels than the middle-dose group (P<0.05).
CONCLUSIONIL-1, IL-6, IL-16, MIP-1α, MCP-1, and TNF-α play a role in the development and progression of silicosis inflammation. TGF-β may be related to (related to; associated with; correlated with) fibrosis.
Animals ; Bronchoalveolar Lavage Fluid ; chemistry ; Chemokine CCL2 ; metabolism ; Chemokine CCL3 ; metabolism ; Cytokines ; metabolism ; Interleukin-1 ; metabolism ; Interleukin-16 ; metabolism ; Interleukin-6 ; metabolism ; Rats ; Rats, Wistar ; Silicon Dioxide ; toxicity ; Silicosis ; metabolism ; Transforming Growth Factor beta1 ; metabolism
7.Expression and significance of pulmonary surfactant protein D and IL-16 in allergic rhinitis and nasal polyps.
Linghao MENG ; Manying GENG ; Baoxing YAN ; Xing LU
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2013;27(5):233-236
OBJECTIVE:
To detect the expression and distribution of the lung surfactant protein D (surfactant protein D,SP-D ) and IL-16 in nasal mucosa of allergic rhinitis and nasal polyps, and then probe into their significance in the pathology of allergic rhinitis and nasal polyps.
METHOD:
Fifteen cases of allergic rhinitis, fifteen cases of nasal polyps and fifteen cases of inferior turbinate mucosa were studied to detect the expression of SP-D and IL-16 by immunohistochemistry method.
RESULT:
The expression of SP-D and IL-16 in allergic rhinitis and nasal polyps were dramatically higher in controls (P < 0.01). There was no remarkable difference in the expression of SP-D and IL-16 between allergic rhinitis and nasal polyps (P > 0.05).
CONCLUSION
Both normal tissue and diseased tissue express SP-D and IL-16. SP-D is likely to play key roles in the inflammatory reaction process of allergic rhinitis and nasal polyps. IL-16 is an important eosinophil chemokine in the process of allergic rhinitis and nasal polyps,and it can also enhance the local role of eosinophils,thus it can involve in the process of allergic rhinitis and nasal polyps disease.
Adolescent
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Adult
;
Female
;
Humans
;
Interleukin-16
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metabolism
;
Male
;
Middle Aged
;
Nasal Polyps
;
metabolism
;
pathology
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Pulmonary Surfactant-Associated Protein D
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metabolism
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Rhinitis, Allergic
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Rhinitis, Allergic, Perennial
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metabolism
;
pathology
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Young Adult
8.Cellular sources of interleukin 16 in benign and malignant pleural effusions.
Jian-Jun LI ; Wei WEI ; Huan-Zhong SHI ; Ying-Xin LI ; Wu-Ning MO
Chinese Medical Journal 2011;124(24):4160-4165
BACKGROUNDInterleukin 16 (IL-16) can be detected by ELISA in pleural effusion (PE) and its concentration is higher than in serum. This study investigated the cellular sources of IL-16 in PE.
METHODSThe samples of PE were collected from 34 patients who were newly diagnosed having PE in the pleural cavity. We performed cell culture to purify the pleural mesothelial cells (PMC), Wright staining to count the purity and immunocytochemical stain to identify the cultured cells. The intracellular IL-16 expression was detected by flow cytometry (FCM). The different cells in PE were first separated by magnetic cell sorting (MCAS) then the separated cells were cultured in RPMI1640 with 10% fetal calf serum (FCS). We extracted the supernatant and detected IL-16 concentration by ELISA. The IL-16 protein was detected by immunohistochemistry and double immunofluorescence staining.
RESULTSThe percentages of cells which secreted IL-16 were: CD3(+)CD8(-) cells ((74.27 ± 15.56)%, n = 34); CD3(+)CD8(+) cells ((69.86 ± 18.55)%, n = 34); CD19(+) cells ((45.30 ± 18.77)%, n = 15); CD14(+) cells ((16.91 ± 16.69)%, n = 15); and PMC ((2.05 ± 1.85)%, n = 7). The concentrations of IL-16 in the supernatant from cultured cells were: CD4(+) cells ((102.50 ± 42.51) ng/L, n = 5); CD8(+) cells ((92.58 ± 18.34) ng/L, n = 5); CD19(+) cells ((79.85 ± 5.62) ng/L, n = 5); CD14(+) cells ((58.51 ± 25.38) ng/L, n = 5); and PMC ((18.14 ± 8.37) ng/L, n = 5). In lymphocytes, monocytes/macrophages and PMC, we could observe the cells that expressed IL-16 protein. In paraffin-embedded sections, we also could observe by immunohistochemistry the CD4(+)IL-16(+) cells, CD8(+)IL-16(+) cells, CD19(+)IL-16(+) cells, and CD14(+)IL-16(+) cells.
CONCLUSIONSIL-16 in PE is mainly secreted by T lymphocytes, including CD3(+)CD8(-) cells and CD3(+)CD8(+) cells. CD19(+) cells and CD14(+) cells can also secrete IL-16, but the percentage of PMC that can secrete IL-16 is very low.
Adult ; Aged ; Aged, 80 and over ; Antigens, CD19 ; metabolism ; CD4-Positive T-Lymphocytes ; metabolism ; CD8-Positive T-Lymphocytes ; metabolism ; Cells, Cultured ; Centrifugation, Density Gradient ; Enzyme-Linked Immunosorbent Assay ; Female ; Flow Cytometry ; Humans ; Immunohistochemistry ; Interleukin-16 ; metabolism ; Lipopolysaccharide Receptors ; metabolism ; Male ; Middle Aged ; Pleural Effusion, Malignant ; metabolism ; T-Lymphocytes ; metabolism ; Young Adult
9.Myeloid differentiation primary response protein 88 blockade upregulates indoleamine 2,3-dioxygenase expression in rheumatoid synovial fibroblasts.
Mi Kyung PARK ; Hye Jwa OH ; Yang Mi HEO ; Eun Mi PARK ; Mi La CHO ; Ho Youn KIM ; Sung Hwan PARK
Experimental & Molecular Medicine 2011;43(8):446-454
Indoleamine 2,3-dioxygenase (IDO) is a key negative regulator of immune responses and has been implicated in tumor tolerance, autoimmune disease and asthma. IDO was detected in the joint synovial tissue in the inflammatory microenvironment of rheumatoid arthritis (RA), but IDO expression in joint synovial tissue is not sufficient to overcome the inflamed synovial environment. This study aimed to unravel the mechanisms involving the failure to activate tolerogenic IDO in the inflamed joint. We demonstrate that both poly (I:C) and lipopolysaccharide (LPS) induce expression of IDO in synovial fibroblasts. However, inflammatory cytokines such as IL-17, TNF-alpha, IL-12, IL-23 and IL-16 did not induce IDO expression. Poly (I:C) appeared to induce higher IDO expression than did LPS. Surprisingly, toll-like receptor (TLR)4-mediated IDO expression was upregulated after depletion of myeloid differentiation primary response protein 88 (MyD88) in synovial fibroblasts using small interfering RNA (siRNA). IDO, TLR3 and TLR4 were highly expressed in synovial tissue of RA patients compared with that of osteoarthritis patients. In addition, RA patients with severe disease activity had higher levels of expression of IDO, TLR3 and TLR4 in the synovium than patients with mild disease activity. These data suggest that upregulation of IDO expression in synovial fibroblasts involves TLR3 and TLR4 activation by microbial constituents. We showed that the mechanisms responsible for IDO regulation primarily involve MyD88 signaling in synovial fibroblasts, as demonstrated by siRNA-mediated knockdown of MyD88.
Adaptor Proteins, Vesicular Transport/genetics/metabolism
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Arthritis, Rheumatoid/*metabolism
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Blotting, Western
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Cells, Cultured
;
Fibroblasts/drug effects/*metabolism
;
Humans
;
Immunohistochemistry
;
Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics/*metabolism
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Interleukin-12/pharmacology
;
Interleukin-16/pharmacology
;
Interleukin-17/pharmacology
;
Interleukin-23/pharmacology
;
Lipopolysaccharides/pharmacology
;
Myeloid Differentiation Factor 88/genetics/*metabolism
;
Poly I-C/pharmacology
;
Polymerase Chain Reaction
;
RNA, Small Interfering/genetics/physiology
;
Synovial Membrane/*cytology
;
Toll-Like Receptor 4/genetics/metabolism
;
Tumor Necrosis Factor-alpha/pharmacology
10.Serum cytokine profiling of prostate cancer and benign prostatic hyperplasia using recombinant antibody microarray.
Lei ZHANG ; Sheng-Kun SUN ; Li-Xin SHI ; Xu ZHANG
National Journal of Andrology 2010;16(7):584-588
OBJECTIVETo identify the differential expressions of serum cytokines between prostate cancer (PCa) and benign prostatic hyperplasia (BPH), and provide proteomic evidence for the early diagnosis of PCa.
METHODSWe used human cytokine array to determine the profiles of the serum cytokines obtained from 6 PCa and 6 BPH patients with the PSA level within the grey scale of 4 - 10 ng/ml.
RESULTSWe identified 19 differentially expressed cytokines in the PCa patients, 16 obviously up-regulated, including IL-3, IL-6 and IL-16, and 3 markedly down-regulated, which were Fas/TNFRSF6, TRALR-3 and IGFBP-6. Most of them were involved in such cellular bioprocesses as transcription, proliferation, signal transduction, and apoptosis.
CONCLUSIONThe cytokine antibody assay permits simultaneous measurement of multiple markers in a small volume of serum, and can identify a panel of key cytokines related to the malignant biological behavior of cancer cells. And it helps to find the biomarkers for the early diagnosis, efficacy assessment and prognosis of prostate cancer.
Aged ; Humans ; Interleukin-16 ; blood ; Interleukin-3 ; blood ; Interleukin-6 ; blood ; Male ; Middle Aged ; Prostatic Hyperplasia ; blood ; genetics ; metabolism ; Prostatic Neoplasms ; blood ; genetics ; metabolism ; Proteomics

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