The Metabolome of Carbapenem-Resistant Klebsiella pneumoniae Infection in Plasma.

AIM: Carbapenem-resistant Klebsiella pneumoniae- (CR-Kp-) mediated infections represent a challenge for clinical practitioners due to their expanding prevalence in hospital environments and antibiotic resistance. However, few studies have shown metabolic changes of carbapenem-resistant Klebsiella pneumoniae and CR-Kp-negative patients, and relevant studies are urgently needed. METHODS: In this study, we comprehensively profile the metabolites of 20 CR-Kp-positive and 18 CR-Kp-negative patients in plasma by using 2D gas chromatography-time-of-flight mass spectrometry (GC×GC-TOFMS). RESULTS: We identified 58 metabolites that were carbapenem-resistant Klebsiella pneumoniae-associated. N-Acetyl glucosamine, butanedioic acid, and myoinositol play a significant character in CR-Kp infection. CONCLUSIONS: Our study provides valuable data to serve as potential targets for developing therapies against CR-Kp infection.

Lack of Efficacy of Combined Carbohydrate Antigen Markers for Lung Cancer Diagnosis.

BACKGROUND: Lung cancer (LC) is top-ranked in cancer incidence and is the leading cause of cancer death globally. Combining serum biomarkers can improve the accuracy of LC diagnosis. The identification of the best potential combination of traditional tumor markers is essential for LC diagnosis. Patients and Methods. Blood samples were collected from 132 LC cases and 118 benign lung disease (BLD) controls. The expression levels of ten serum tumor markers (CYFR21, CEA, NSE, SCC, CA15-3, CA 19-9, CA 125, CA50, CA242, and CA724) were assayed, and that the expression in the levels of tumor markers were evaluated, isolated, and combined in different patients. The performance of the biomarkers was analyzed by receiver operating characteristic (ROC) analyses, and the difference between combinations of biomarkers was compared by Chi-square (χ 2) tests. RESULTS: As single markers, CYFR21 and CEA showed good diagnostic efficacy for nonsmall cell lung cancer (NSCLC) patients, while NSE and CEA were the most sensitive in the diagnosis of small cell lung cancer (SCLC). The area under the curve (AUC) value was 0.854 for the panel of four biomarkers (CYFR21, CEA, NSE, and SCC), 0.875 for the panel of six biomarkers (CYFR21, CEA, NSE, SCC, CA125, and CA15-3), and 0.884 for the panel of ten markers (CYFR21, CEA, NSE, SCC, CA125, CA15-3, CA19-9, CA50, CA242, and CA724). With a higher sensitivity and negative predictive value (NPV), the diagnostic accuracy of the three panels was better than that of any single biomarker, but there were no statistically significant differences among them (all P values > 0.05). However, the panel of six carbohydrate antigen (CA) biomarkers (CA125, CA15-3, CA19-9, CA50, CA242, and CA724) showed a lower diagnostic value (AUC: 0.776, sensitivity: 59.8%, specificity: 73.0%, and NPV: 60.4%) than the three panels (P value < 0.05). The performance was similar even when analyzed individually by LC subtypes. CONCLUSION: The biomarkers isolated are elevated for different types of lung cancer, and the panel of CYFR21, CEA, NSE, and SCC seems to be a promising serum biomarker for the diagnosis of lung cancer, while the combination with carbohydrate antigen markers does not improve the diagnostic efficacy.

Inhibition of lung cancer cells and Ras/Raf/MEK/ERK signal transduction by ectonucleoside triphosphate phosphohydrolase-7 (ENTPD7).

BACKGROUND: The aim of this study was to investigate the effects and mechanisms of ectonucleoside triphosphate phosphohydrolase-7 (ENTPD7) on lung cancer cells. METHODS: The expression characteristics of ENTPD7 and its effect on the survival of lung cancer patients were analyzed by referring to The Cancer Genome Atlas (TCGA). Streptavidin-peroxidase (SP) staining was performed to detect the ENTPD7 protein in tumor tissues and adjacent tissues. Plasmid transfection technology was also applied to silence ENTPD7 gene. Crystal violet staining and flow cytometry were performed to determine cell proliferation and apoptosis. Tumor-bearing nude mice model was established to investigate the effect of sh-ENTPD7 on tumors. RESULTS: The results showed that patients with low levels of ENTPD7 had higher survival rates. ENTPD7 was up-regulated in lung cancer tissues and cells. Down-regulation of the expression of ENTPD7 inhibited proliferation but promoted apoptosis of lung cancer cell. Silencing ENTPD7 also inhibited the expression levels of Ras and Raf proteins and the phosphorylation of mitogen-activated protein kinase (MEK) and extracellular signal-regulated kinase (ERK). Tumor-bearing nude mice experiments showed that silencing ENTPD7 had an inhibitory effect on lung cancer cells. CONCLUSIONS: ENTPD7 was overexpressed in lung cancer cells. Down-regulating ENTPD7 could inhibit lung cancer cell proliferation and promote apoptosis via inhibiting the Ras/Raf/MEK/ERK pathway.

Molecular mechanisms of microRNAs in regulating epithelial-mesenchymal transitions in human cancers.

The epithelial-mesenchymal transition (EMT) provides a strong driving force in the progression of various human cancers and the development of chemoresistance. Recently, numbers of studies have demonstrated that microRNAs (miRNAs), by post-transcriptionally silencing EMT-related molecules, can promote or inhibit the EMT process and play pivotal roles in effectively manipulating the occurrence, development, invasion, and metastasis of cancers. MiRNAs can also control the EMT or be controlled by genetic modification and mutual regulation, especially negative feedback. Therefore, miRNAs can be viewed as either oncogenes or tumor suppressor genes to facilitate or retard the EMT, resulting in far-reaching impact on tumor metastasis and effective diagnosis, treatment, and prognosis.