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Background: Combination chemotherapy with Western anti-tuberculosis (TB) drugs is the mainstay of TB treatment. Chinese herbal medicines with either heat clearing and detoxifying effects or nourishing Yin and reducing fire effects have been used to treat TB based on the Traditional Chinese Medicine (TCM) syndromes of TB patients. This study analyzed the expression profiles of long non-coding RNAs (lncRNAs) and mRNAs in TB patients with different TCM syndromes. Methods: TB patients were classified as pulmonary Yin deficiency (PYD) syndrome, hyperactivity of fire due to Yin deficiency (HFYD) syndrome, and deficiency of Qi and Yin (DQY) syndrome. Total RNA from 44 TB patients and healthy controls was extracted and hybridized with a human lncRNA microarray containing 30586 lncRNAs and 26109 mRNAs probes. Bioinformatics analyses, including gene ontology (GO) and pathways, were performed. Related clinical data were also analyzed. Results: Differentially expressed mRNAs and lncRNAs were identified (fold change >2, and P < 0.05) in PYD (634 mRNAs and 566 lncRNAs), HFYD (47 mRNAs and 55 lncRNAs), and DQY (63 mRNAs and 60 lncRNAs) patients. The most enriched pathways were the hippo signaling pathway (P = 0.000164) and the protein digestion and absorption pathway (P = 5.89017E-05). Clinical analyses revealed that the lipid indexes of TB patients were abnormal and that the triglyceride concentration was significantly higher in DQY patients (P = 0.0252). Our study is the first to acquire the microarray expression profiles of lncRNAs and mRNAs and analyze pathway enrichment in PYD, HFYD, and DQY patients with TB. Conclusions: Our analyses of the expression profiles of lncRNAs and mRNAs may represent a novel method to explore the biological essence of TCM syndromes of TB. [ABSTRACT FROM AUTHOR]

Background: Traditional Chinese Medicine (TCM) has been applied in treating tuberculosis (TB) based on the TCM syndromes with the effects of inhibiting Mycobacterium, strengthening the body immune system, and reducing the pulmonary toxicity. We used bioinformatic methods to study the clinical and pathological characteristics of pulmonary TB patients with TCM syndromes. Isobaric tags for relative and absolute quantification - coupled two dimensional liquid chromatography-tandem mass spectrometry (iTRAQ-2DLC-MS/MS) methods were applied to screen differentially expressed serum proteins. Methods: Pulmonary TB cases were divided into four distinctive TCM syndromes: pulmonary Yin deficiency (PYD) syndrome, hyperactivity of fire due to Yin deficiency (HFYD) syndrome, deficiency of Qi and Yin (DQY) syndrome, and deficiency of Yin and Yang (DYY) syndrome. The serum samples from 214 pulmonary TB patients were collected, and the clinical and pathological data was analyzed by using iTRAQ-2DLC-MS/MS. Finally, the differentially expressed proteins were screened and tested by ELISA. Only 5 patients with DYY syndrome were recruited in 3 years, which were not enough for further research. Results: The DQY cases had higher erythrocyte sedimentation rate (ESR) compared to the PYD and HFYD cases (P = 0.0178). 94.44 % (12 PYD, 18 HFYD, and 4 DQY before anti-TB treatment) of 36 treated TB cases were transformed to PYD accompanied with the reduction of ESR and absorption of pulmonary lesions. A total of 39 differentially expressed proteins (ratios of >1.3 or <0.75) were found among the three TCM syndromes. Proteomic studies revealed that gamma-glutamyl hydrolase (GGH), Ig gamma-3 chain C region (IGHG3), and haptoglobin (HPT) were specifically over-expressed in PYD (P< 0.01), HFYD (P< 0.001), and DQY cases (P< 0.01), respectively. Furthermore, GGH was significantly higher in PYD cases compared to the HFYD and DQY cases (P< 0.01, P < 0.001, respectively), whereas IGHG3 was significantly higher in HFYD cases than PYD and DQY cases (P< 0.001, P< 0.01, respectively). Conclusions: The results suggest that TCM syndromes are significantly correlated with the pulmonary lesions and ESR. GGH was associated with folate metabolism in PYD cases, IGHG3 was linked to the control of Mycobacterium infection in HFYD patients, and HPT was involved in hypoxia in DQY patients. The present study provides new biological basis to understand the pathological changes and proteomic differences of TB syndromes. [ABSTRACT FROM AUTHOR]

Background: Single nucleotide polymorphisms (SNPs) within precursor microRNAs (miRNAs) can affect miRNAs expression, and may be involved in the pathogenesis of pulmonary tuberculosis (TB). This study aimed to investigate potential associations between the four precursor miRNA SNPs (miR-146a C > G, miR-149 T > C, miR-196a2 T > C, and miR-499 T > C) and susceptibility to pulmonary TB in the Chinese Uygur, Kazak, and Southern Han populations. Methods: A case-control study was performed on Chinese Uygur (n = 662), Kazak (n = 612), and Southern Han (n = 654) populations using the PCR-PFLR method. The allele and genotype frequencies for all populations were analyzed. Linkage disequilibrium was performed, and different models of inheritance were tested. Results: The allele and genotype frequencies of the miR-499 SNP were significantly different between the TB patients group and the healthy control group in the Uygur population, and were found to be codominant, dominant, recessive and additive models in association with pulmonary TB. The haplotype CTCC showed significant correlation with pulmonary TB. The allele and genotype frequencies of miR-146a and miR-196a2 SNPs were significantly different between the two groups in the Kazak population. The miR-146a SNP was found to be codominant, recessive and additive models, whereas, the miR-196a2 SNP was found to be codominant, dominant, and additive models in association with pulmonary TB. The haplotypes TCCC and CCCT showed significant correlation with pulmonary TB. Conclusions: The results suggested that susceptibility to pulmonary TB may be closely related to individual differences caused by genetic factors among different ethnic groups in China. [ABSTRACT FROM AUTHOR]

Background Mycobacterium tuberculosis infection can activate the immune system, leading to characteristic pathological changes such as inflammatory granuloma, caseous necrosis, and cavity formation. Methods Clinical data of 187 cases of pulmonary tuberculosis (PTB) were analyzed using statistical methods, while serum levels of complement C4b (C4b), fibronectin (FN), and prolidase (PEPD) were detected using the ELISA method among the control, minimal PTB, moderate PTB, and advanced PTB groups. Results We found significantly higher levels of serum C4b and PEPD (P = 0.018, P = 0.003), and significantly lower levels of serum FN (P < 0.001) in PTB patients. Furthermore, the serum levels of 3 proteins were significantly different among 3 PTB groups. FN level was significantly higher in the moderate PTB group, compared with patients in the minimal and advanced PTB groups (P < 0.05, P < 0.01). PEPD level was significantly higher in the moderate PTB group, compared with the minimal PTB group (P < 0.05). Analysis of clinical data showed that serum albumin, C-reactive protein (CRP), prealbumin, and C4 were significantly higher (P < 0.05), while serum globulin was significantly lower in patients with PTB (P < 0.001). A significant negative correlation was found between C4b and albumin, prealbumin. On the other hand, a significant positive correlation was found between C4b and globulin, CRP, PEPD, as well as between PEPD and CRP (P < 0.05). Conclusions Our study showed that C4b, FN, and PEPD are associated with tissue damage, granuloma formation, and cavity formation, respectively, in patients with PTB. The present study provides a new experimental basis to understand the pathogenesis and pathological changes of PTB. [ABSTRACT FROM AUTHOR]

Background Noninvasive and convenient biomarkers for early diagnosis of tuberculosis (TB) remain an urgent need. The aim of this study was to discover and identify potential biomarkers specific for TB. Methods The surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDITOF MS) combined with weak cation exchange (WCX) magnetic beads was used to screen serum samples from 180 cases of TB and 211 control subjects. A classification model was established by Biomarker Pattern Software (BPS). Candidate protein biomarkers were purified by reverse phase-high performance liquid chromatography (RP-HPLC), identified by MALDI-TOF MS, LC-MS/MS and validated using enzyme-linked immunosorbent assay (ELISA). Results A total of 35 discriminating m/z peaks were detected that were related to TB (P < 0.01). The model of biomarkers based on the four biomarkers (2554.6, 4824.4, 5325.7, and 8606.8 Da) was established which could distinguish TB from controls with the sensitivity of 83.3% and the specificity of 84.2%. The candidate biomarker with m/z of 2554.6 Da was found to be upregulated in TB patients, and was identified as a fragment of fibrinogen, alpha polypeptide isoform alpha-E preproprotein. Analysis in 22 patients with TB showed increased fibrinogen degradation product (FDP) (5,005 ± 1,297 vs. 4,010 ± 1,181 ng/mL, P < 0.05) and in 142 patients showed elevated plasma fibrinogen levels. Conclusions A diagnostic model for TB with high sensitivity and specificity was developed using mass spectrometry combined with magnetic beads. Fibrinogen was identified as a potential biomarker for TB and showed diagnostic values in clinical application. [ABSTRACT FROM AUTHOR]