The epidemic of pulmonary tuberculosis (TB), especially multidrug-resistance tuberculosis (MDR-TB) presented a major challenge for TB treatment today.We performed iTRAQ labeling coupled with two-dimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS) and Solexa sequencing among MDR-TB patients, drug-sensitive tuberculosis (DS-TB) patients, and healthy controls.A total of 50 differentially expressed proteins and 43 differentially expressed miRNAs (fold change >1.50 or <0.60, P<0.05) were identified in the MDR-TB patients compared to both DS-TB patients and healthy controls.We found that 22.00% of differentially expressed proteins and 32.56% of differentially expressed miRNAs were related, and could construct a network mainly in complement and coagulation cascades.Significant differences in CD44 antigen (CD44), coagulation factor XI (F11), kininogen-1 (KNG1), miR-4433b-5p, miR-424-5p, and miR-199b-5p were found among MDR-TB patients, DS-TB patients and healthy controls (P<0.05)by enzyme-linked immunosorbent assay (ELISA) and SYBR green qRT-PCR validation.A strong negative correlation, consistent with the target gene prediction, was found between miR-199b-5p and KNG1 (r=-0.232,P=0.017).Moreover, we established the MDR-TB diagnostic model based on five biomarkers (CD44, KNG1, miR-4433b-5p, miR-424-5p, and miR-199b-5p).Our study proposes potential biomarkers for MDR-TB diagnosis, and also provides a new experimental basis to understand the pathogenesis of MDR-TB.
Yin and Yang are the two counter-balancing aspects in ancient Chinese philosophy. In traditional Chinese medicine, Yin deficiency syndrome (YDS) is a common sub-health state with complex causes. While the syndrome may be treated to various degrees of effectiveness with traditional Chinese medicine, efficient modern methods are yet to be developed for diagnosing and treating the YDS. Here we performed a metabolomics study on YDS in rats. Serum metabolites in rats were analyzed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) method to identify potential biomarkers for YDS. The rats were divided randomly into the healthy control group, the untreated YDS group, and the anemarrhena treated YDS group. Compared with the control group, significant increase in the metabolites such as dihydrotestosterone (DHT) and 5β-DHT, 4-imidazolone-5-propanoate, 4-(L-alanin-3-yl)-2-hydroxy-cis,cis-muconate 6-semialdehyde, and 5-(L-alanin-3-yl)-2-hydroxy-cis,cis-muconate 6-semialdehyde were observed in the serum of untreated YDS group, which returned to normal in the anemarrhena treated group. Therefore, these metabolites may serve as potential biomarkers for YDS, and may facilitate the diagnosis and treatment of YDS.
The aim of this study is to investigate the effect of monoammonium glycyrrhizinate (MAG) on lipopolysaccharide (LPS) -induced acute lung injury (ALI) and its anti-inflammatory mechanism in mice. All male ICR mice were randomly divided into six groups: LPS group; control group; MAG 3, 10, and 30 mg x kg(-1) groups; and dexamethasone (DXM) 5 mg x kg(-1) group. Lung dry weight and wet weight percentage and permeability were detected. Neutrophil infiltration in bronchoalveolar lavage fluid (BALF) and lung tissues was detected by cell count and morphological analysis. The levels of TNF-alpha and IL-10 in lung were detected by ELISA. MPO activity was determined followed the specification. MAG induced a decrease in lung wet weight/dry weight ratio, and significantly decreased in total leucocyte number and neutrophil percentage in the BALF, and MPO activity of lung in a dose-dependent manner. Importantly, It could up-regulate the IL-10 level and down-regulate the TNF-alpha level in the lung tissue of ALI mice. These results suggested that the protective effect of MAG in mice on LPS induced ALI was associated with the regulation of TNF-alpha/IL-10 balance, and MAG maybe a potentially treatment for ALI/ARDS.
The epidemic of pulmonary tuberculosis (TB), especially multidrug‐resistance tuberculosis (MDR‐TB) presented a major challenge for TB treatment today. We performed iTRAQ labeling coupled with two‐dimensional liquid chromatography‐tandem mass spectrometry (2D LC‐MS/MS) and Solexa sequencing among MDR‐TB patients, drug‐sensitive tuberculosis (DS‐TB) patients, and healthy controls. A total of 50 differentially expressed proteins and 43 differentially expressed miRNAs (fold change >1.50 or <0.60, P <0.05) were identified in the MDR‐TB patients compared to both DS‐TB patients and healthy controls. We found that 22.00% of differentially expressed proteins and 32.56% of differentially expressed miRNAs were related, and could construct a network mainly in complement and coagulation cascades. Significant differences in CD44 antigen (CD44), coagulation factor XI (F11), kininogen‐1 (KNG1), miR‐4433b‐5p, miR‐424‐5p, and miR‐199b‐5p were found among MDR‐TB patients, DS‐TB patients and healthy controls ( P <0.05) by enzyme‐linked immunosorbent assay (ELISA) and SYBR green qRT‐PCR validation. A strong negative correlation, consistent with the target gene prediction, was found between KNG1 and miR‐199b‐5p (r=−0.232, P =0.017). Moreover, we established a diagnostic model for MDR‐TB patients and healthy controls with a sensitivity of 100.00% and a specificity of 88.33% (overall accuracy 93.14%), and also established a diagnostic model for MDR‐TB patients and DS‐TB patients with a sensitivity of 83.33% and a specificity of 88.33% (overall accuracy 86.27%). Our study proposes potential biomarkers for MDR‐TB diagnosis, and also provides a new experimental basis to understand the pathogenesis of MDR‐TB. Support or Funding Information This work was supported by grants from the National Natural Science Foundation of China (No.81573709, No.81273882), the National Basic Research Program of China (No.2014CB543002) and the National Special Sci‐Tech Projects (No.2012ZX10005001‐006).
This study aims to explore the effect of Zhibai Dihuang Granule (ZDG) on anti‐inflammatory proteins in the serum of Yin deficiency heat syndrome rats. The Yin deficiency syndrome rat model was established by triiodothyronine, and differentially expressed proteins in the serum of rats were analyzed by iTRAQ. The levels of anti‐inflammatory proteins such as Gelsolin (Gsn), Plasminogen (Plg), Fibrinogen alpha chain (Fga), and Thymosin beta‐4 (T‐β4) were significantly increased in the ZDG treated model rats, compared with the control rats. However, the level of Coagulation factor XIII A chain was significantly decreased in the ZDG treated group. Gsn has been found to remove the damaged tissue and release actin, thereby inhibiting cell apoptosis. Gsn was significantly increased in the ZDG treated group, indicating that ZDG may affect Gsn to inhibit cell apoptosis. Colla2 and Plg have been shown to regulate the blood rheology in the inflammatory response. Colla2 was significantly decreased and Plg wes significantly increased in the ZDG treated group, suggesting that ZDG can regulate the blood rheology of the inflammatory response by down‐regulating the Colla2 and up‐regulating Plg. Gsn and T‐β4 have been shown to promote the healing of inflammatory damage by regulating cytokines. Gsn and T‐β4 were significantly increased in the ZDG treated group, indicating that ZDG could inhibit apoptosis by regulating cytokines. Conclusion ZDP can treat Yin deficiency heat syndrome by removing damaged tissue, releasing actin and lipopolysaccharide, inhibiting cell apoptosis, regulating inflammatory factors and the blood rheology of inflammation, and promoting the healing of inflammatory damage. Support or Funding Information This work was supported by grants from the National Basic Research Program of China (No.2014CB543002), the National Natural Science Foundation of China (No.81573709, No.81273882)
Rapid and efficient methods for the determination of cured tuberculosis (TB) are lacking. A total of 85 differentially expressed serum proteins were identified by iTRAQ labeling coupled with two-dimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS) analysis (fold change >1.50 or <0.60, P < 0.05). We validated albumin (ALB), Rho GDP-dissociation inhibitor 2 (ARHGDIB), complement 3 (C3), ficolin-2 (FCN2), and apolipoprotein (a) (LPA) using the enzyme-linked immunosorbent assay (ELISA) method. Significantly increased ALB and LPA levels (P = 0.036 and P = 0.012, respectively) and significantly reduced ARHGDIB, C3, and FCN2 levels (P < 0.001, P = 0.035, and P = 0.018, respectively) were observed in cured TB patients compared with untreated TB patients. In addition, changes in ALB and FCN2 levels occurred after 2 months of treatment (P < 0.001 and P = 0.030, respectively). We established a cured TB model with 87.10% sensitivity, 79.49% specificity, and an area under the curve (AUC) of 0.876. The results indicated that ALB, ARHGDIB, C3, FCN2, and LPA levels might serve as potential biomarkers for cured TB. Our study provides experimental data for establishing objective indicators of cured TB and also proposes potential markers for evaluating the efficacy of anti-TB drugs.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)