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OBJECTIVE@#To screen new serum metabolic biomarkers for different drug resistance profiles of pulmonary tuberculosis (TB) and explore their mechanisms and functions.@*METHODS@#We collected serum samples from TB patients with drug sensitivity (DS), monoresistance to isoniazid (MR-INH), monoresistance to rifampin (MR-RFP), multidrug resistance (MDR), and polyresistance (PR). The metabolites in the serum samples were extracted by oscillatory and deproteinization for LC-MS/MS analysis, and the results were normalized by Pareto-scaling method and analyzed using Metaboanalyst 4.0 software to identify the differential metabolites. The differential metabolites were characterized by function enrichment and co-expression analysis to explore their function and possible pathological mechanisms.@*RESULTS@#Compared with the DS group, 286 abnormally expressed metabolites were identified in MR-INH group, 362 in MR-RPF group, 277 in MDR group and 1208 in PR group by LC-MS/MS analysis. Acetylagmatine ( < 0.05), aminopentol ( < 0.05), and tetracosanyl oleate ( < 0.05) in MR-INH group; Ala His Pro Thr ( < 0.001) and glycinoprenol-9 ( < 0.05) in MR-RFP group; trimethylamine ( < 0.05), penaresidin A ( < 0.05), and verazine ( < 0.05) in MDR group; and PIP (18:1(11Z)/ 18:3(6Z, 9Z, 12Z)) ( < 0.001), Pro Arg Trp Tyr ( < 0.001), N-methyldioctylamine ( < 0.001), and phytolaccoside E ( < 0.05) in PR group all showed significant differential expressions. Significant differential expressions of phthalic acid mono-2-ethylhexyl ester ( < 0.05) and eicosanoyl-EA ( < 0.05) were found in all the drug resistant groups as compared with DS group.@*CONCLUSIONS@#Acetylagmatine, aminopentol, tetracosanyl oleate, Ala His Pro Thr, glycinoprenol-9, trimethylamine, penaresidin A, verazine, PIP(18:1(11Z)/18:3(6Z, 9Z, 12Z)), Pro Arg Trp Tyr, N-methyldioctylamine, phytolaccoside E, phthalic acid mono-2-ethylhexyl ester, and eicosanoyl-EA are potentially new biomarkers that indicate monoresistance, multi-drug resistance and polyresistance of Mycobacterium tuberculosis. The combined use of these biomarkers potentially allows for assessment of drug resistance in TB and enhances the diagnostic sensitivity and specificity.
Subject(s)
Humans , Biomarkers , Chromatography, Liquid , Tandem Mass Spectrometry , Tuberculosis, Multidrug-Resistant , Tuberculosis, PulmonaryABSTRACT
Objective To study serum IL-22 levels in patients with pulmonary tuberculosis and diabetes mellitus (PPTDM) and to analysis their clinical significance.Methods ELISA was used to detect serum IL-22 levels in 30 cases PPTDM pa-tients,30 cases pulmonary tuberculosis (PTB)patients,30 cases diabetes mellitus (DM)patients and 30 cases healthy vol-unteers (HV).Results Serum IL-22 levels of PPTDM patients (54.4±4.81 pg/ml)were significantly lower than those in diabetes mellitus (DM)patients (72.36±5.12 pg/ml)and healthy volunteers (HV)(68.32±3.08 pg/ml)(t=2.557,P =0.013;t=2.437,P =0.018),respectively.There was no significantly different of serum IL-22 levels between PPTDM and PTB patients (t=1.190,P =0.239).Serum IL-22 levels of diabetes mellitus coincident with pulmonary tuberculosis (DM-PTB)patients (64.62±8.59 pg/ml)were significantly higher than those in pulmonary tuberculosis coincident with diabetes mellitus (PTB-DM)patients (44.21±2.68 pg/ml)(t=2.267,P =0.031).Conclusion IL-22 may play an important role in PPTDM development.
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Objective To detect plasma interleukins-35 (IL-35 )level in the patients with active tuberculosis complicated with bronchiectasis and to analyze its clinical significance.Methods Peripheral blood of patients with active tuberculosis from depart-ment of Dongguan 6th People′s hospital were collected,assigned to the active tuberculosis complicated with bronchiectasis group and active tuberculosis group.The healthy volunteers served as the control group.The plasma IL-35 level was measured by ELISA, and peripheral blood neutrophils and lymphocytes were detected by hematology analyzer.Results The levels of plasma IL-35 signif-icantly increased in both patients with active tuberculosis complicated with bronchiectasis and patients with active tuberculosis.The level of plasma IL-35 of patients with active tuberculosis complicated with bronchiectasis was significantly higher than that of the patients with active tuberculosis.The absolute value and percentage of peripheral blood neutrophils of patients with active tubercu-losis complicated with bronchiectasis were significantly higher than those of healthy volunteers.However,the percentage of periph-eral blood lymphocytes of patients with active tuberculosis complicated with bronchiectasis was significantly lower than that of healthy volunteers.Pearson correlation analysis showed that the absolute value of peripheral blood neutrophils of patients with ac-tive tuberculosis was positively correlated to the level of plasma IL-35.Conclusion IL-35 may play an important role in the progres-sion of active tuberculosis complicated with bronchiectasis.The determination of IL-35 may be helpful to the diagnosis of patients with active tuberculosis complicated with bronchiectasis.