Diagnosis of parapneumonic pleural effusion with serum and pleural fluid Activin A.

OBJECTIVE: The aim is to evaluate the diagnostic value of Activin A levels in serum and pleural fluid on Parapneumonic Pleural Effusion (PPE). METHODS: The authors collected serum and pleural fluid from 86 PPE and 37 Non-PPE (NPPE) patients. Including Activin A, levels of biomarkers such as Lactate Dehydrogenase (LDH), Procalcitonin (PCT), and C-Reactive Protein (CRP) were measured. All factors were calculated for association with days after admission. The diagnostic potential of biomarkers on PPE was considered by Receiver Operating Characteristic (ROC) curve analysis. RESULTS: Levels of Activin A in serum and pleural fluid of PPE patients were significantly higher than those of the NPPE patients. Moreover, concentrations of Activin A in pleural fluid showed a more obvious relevant days after admission. ROC curve analysis found that Activin A in pleural fluid had AUCs of 0.899 with 93% sensitivity and 84% specificity for PPE diagnosis. CONCLUSION: Activin A in pleural fluid correlated with disease severity could act to diagnose PPE.

Increased progranulin as an independent predictive biomarker for poor prognosis in sepsis.

BACKGROUND: Recently, many diagnostic biomarkers were reported, but each had its own limitation. However, there is a need for an effective sensitivity and specificity of biomarker in diagnosis and prognosis of sepsis. In this context, progranulin (PGRN), at elevated levels, has been associated with poor prognosis in infectious diseases. Moreover, increased PGRN levels were seen in septic mice. As the prognostic value of PGRN in humans is unclear, we aimed to identify the predictive value of serum PGRN for the prognosis of sepsis. METHODS: A total of 128 participants with sepsis and 58 healthy controls were recruited in this study. The levels of serum PGRN were detected by enzyme-linked immunosorbent assay. According to the outcomes, patients were divided into survival and non-survival groups. RESULTS: Serum PGRN levels had upregulated in patients with sepsis compared with those in healthy controls (P < 0.001) as well as in non­survivors compared with those in survivors (P < 0.001). Furthermore, serum PGRN levels exhibited positive correlation with hypersensitive C-reactive protein, procalcitonin, sepsis­related organ failure assessment (SOFA) scores, and acute physiology and chronic health evaluation II (APACHE II) scores. PGRN had a higher predictive effect, especially the 28-day in-hospital mortality (p < 0.001), when using it with SOFA or APACHE II scores. Cox proportional regression analysis showed that PGRN was an independent predictor for 28-day mortality risk in sepsis. CONCLUSIONS: PGRN, as a biomarker of sepsis, could improve the prognostic power of traditional parameters. This study is the first to report the clinical significance of PGRN levels in terms of the severity and prognosis of sepsis.

Diagnosis of parapneumonic pleural effusion with serum and pleural fluid Activin A

Abstract Objective The aim is to evaluate the diagnostic value of Activin A levels in serum and pleural fluid on Parapneumonic Pleural Effusion (PPE). Methods The authors collected serum and pleural fluid from 86 PPE and 37 Non-PPE (NPPE) patients. Including Activin A, levels of biomarkers such as Lactate Dehydrogenase (LDH), Procalcitonin (PCT), and C-Reactive Protein (CRP) were measured. All factors were calculated for association with days after admission. The diagnostic potential of biomarkers on PPE was considered by Receiver Operating Characteristic (ROC) curve analysis. Results Levels of Activin A in serum and pleural fluid of PPE patients were significantly higher than those of the NPPE patients. Moreover, concentrations of Activin A in pleural fluid showed a more obvious relevant days after admission. ROC curve analysis found that Activin A in pleural fluid had AUCs of 0.899 with 93% sensitivity and 84% specificity for PPE diagnosis. Conclusion Activin A in pleural fluid correlated with disease severity could act to diagnose PPE.

Quantum Dots-Based Point-of-Care Measurement of Procalcitonin in Finger-Prick Blood and Venous Whole Blood Specimens.

OBJECTIVE: To determine whether the performance of a new quantum dots-based point-of-care test (POCT) devices is qualified for procalcitonin testing. METHODS: Finger-prick and venous blood specimens from 153 patients were measured with a quantum dots-based POCT device; the results were compared with those from the reference method. RESULTS: The quantum dots-based POCT device correlated well with the reference method in measuring plasma, venous whole blood, and finger-prick blood. No significant bias was observed (-0.08 ng/mL). At 0.5 ng per mL cutoff value, the concordances were 96.6%, 94.6%, and 90.5% for plasma, venous whole blood, and finger-prick blood, respectively. And at 2 ng per mL cutoff value, the concordances were 98.0%, 96.6%, and 95.3%, respectively. CONCLUSIONS: The quantum dots-based POCT device measured procalcitonin with multiple specimen types, high sensitivity, wide detection range, and short turnaround time. It would allow a more widespread use of procalcitonin and help lessen the burden of overcrowding in healthcare facilities in China.

HEPACAM inhibited the growth and migration of cancer cells in the progression of non-small cell lung cancer.

Hepatocyte cell adhesion molecule (HEPACAM), a member of immunoglobulin superfamily, is an adhesion molecule. Although dysregulation of several adhesion molecules has been implicated in the progression of non-small cell lung cancer (NSCLC), the expression profile and functions of HEPACAM in NSCLC remains unknown. In this study, it was found that the expression of HEPACAM was downregulated in NSCLC tissues. Forced expression of HEPACAM in NSCLC cells inhibited the growth and migration of the cancer cells, while knocking down the expression of HEPACAM promoted cell growth, migration, and metastasis. In the molecular mechanism study, HEPACAM was found to be a negative regulator of beta-catenin/TCF signaling. Taken together, this study revealed the suppressive roles of HEPACAM in NSCLC and restoring the function of HEPACAM in NSCLC might be a promising strategy for the therapy.

Type II, but not type I, cGMP-dependent protein kinase reverses bFGF-induced proliferation and migration of U251 human glioma cells.

Previous data have shown that the type II cGMP­dependent protein kinase (PKG II) inhibits the EGF­induced MAPK signaling pathway. In order to thoroughly investigate PKG, it is necessary to elucidate the function of another type of PKG, PKG I. The aim of this study was to investigate the possible inhibitory effect of PKG II and PKG I activity on the basic fibroblast growth factor (bFGF)­induced proliferation and migration of U251 human glioma cells and the possible underlying mechanisms. U251 cells were infected with adenoviral constructs encoding cDNA of PKG I (Ad­PKG I) or PKG II (Ad­PKG II) to increase the expression levels of PKG I or PKG II and then treated with 8­Br­cGMP and 8­pCPT­cGMP, respectively, to activate the enzyme. An MTT assay was used to detect the proliferation of the U251 cells. The migration of the U251 cells was analyzed using a Transwell migration assay. Western blot analysis was used to detect the phosphorylation/activation of the fibroblast growth factor receptor (FGFR), MEK and ERK and the nuclear distribution of p-ERK. The results showed that bFGF treatment increased the proliferation and migration of U251 cells, accompanied by increased phosphorylation of FGFR, MEK and ERK. Furthermore, the nuclear distribution of p-ERK increased following bFGF treatment. Increasing the activity of PKG II through infection with Ad-PKG II and stimulation with 8-pCPT-cGMP significantly attenuated the aforementioned effects of the bFGF treatment, while increased PKG I activity did not inhibit the effects of bFGF treatment. These data suggest that increased PKG II activity attenuates bFGF­induced proliferation and migration by inhibiting the MAPK/ERK signaling pathway, whereas PKG I does not.

Endogenous cGMP-dependent protein kinase reverses EGF-induced MAPK/ERK signal transduction through phosphorylation of VASP at Ser239.

In our previous study, we demonstrated that type II cGMP-dependent protein kinase (PKG II) was expressed at lower levels in different human cancer cell lines and that exogenous PKG II inhibited epidermal growth factor (EGF)-induced MAPK/ERK signaling. In order to investigate its functions further in this signaling pathway, it is necessary to elucidate whether endogenous PKG has the same effect or not. This study aimed to investigate the possible inhibitory effect of endogenous PKG activity on EGF-induced MAPK/ERK signal transduction in human lung cancer cells and its mechanism. Human small cell lung carcinoma cells (SCLCs) were treated with the PKG-selective cGMP analog 8-pCPT-cGMP to activate endogenous PKG, EGF and cGMP followed by EGF, respectively. The results showed that increased endogenous PKG activity inhibited the EGF-induced phosphorylation of the epidermal growth factor receptor (EGFR) and the binding between Sos1 and Grb2. In addition, EGF-triggered Ras activation was reversed by increased endogenous PKG activity. While the EGF-induced phosphorylation of MEK and ERK were inhibited by increased endogenous PKG activity, there was a significant increase of phosphorylated vasodilator-stimulated phosphoprotein (p-VASP) at Ser239. Furthermore, we investigated whether endogenous PKG exerted its effects on EGF-induced MAPK/ERK signaling through phosphorylation of VASP at Ser239. Downregulation of the levels of p-VASP Ser239 by point mutation blocked the effects of endogenous PKG on EGF-induced MAPK/ERK signal transduction. The data shown here suggest that endogenous PKG reverses the EGF-induced MAPK/ERK signaling pathway by phosphorylating VASP at Ser239.