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Background: Nemonoxacin, a novel nonfluorinated quinolone, has broad-spectrum antibacterial activity, including activity against antibiotic-resistant strains, and was developed for treating community-acquired pneumonia (CAP). This report provides an integrated safety summary of oral nemonoxacin from two phase II and one phase III clinical studies., Methods: Patients with mild CAP were randomized for treatment with nemonoxacin 500 mg (NEMO-500MG), nemonoxacin 750 mg (NEMO-750MG), or levofloxacin 500 mg (LEVO), orally, once daily, for 7-10 days. Hematological, gastrointestinal, and hepatic disorders; electrocardiography abnormalities; and reported quinolone-associated clinical concerns were included in this analysis., Results: A total of 520, 155, and 320 subjects were assigned to receive NEMO-500MG, NEMO-750MG, and LEVO, respectively. The incidence of adverse events (AEs) was the highest (54.8%) in the NEMO-750MG group (NEMO-500MG, 36.9%; NEMO-750MG, 54.8%; LEVO, 39.7%) and that of drug-related AEs was comparable between the three groups (NEMO-500MG, 22.9%; NEMO-750MG, 31.0%; LEVO, 22.5%). The majority (>80%) of the patients showed mild drug-related AEs and the distribution based on severity was similar between the groups. The most commonly reported drug-related AEs included neutropenia (NEMO-500MG, 2.5%; NEMO-750MG, 8.4%; LEVO, 4.4%), nausea (NEMO-500MG, 2.5%; NEMO-750MG, 7.1%; LEVO, 2.5%), leukopenia (NEMO-500MG, 2.3%; NEMO-750MG, 4.5%; LEVO, 3.1%), and increased alanine aminotransferase level (NEMO-500MG, 4.4%; NEMO-750MG, 0%; LEVO, 2.5%)., Conclusion: Nemonoxacin was well tolerated and no clinically significant safety concerns were identified, suggesting that it possesses a desirable safety and tolerability profile similar to that of levofloxacin, and may be a suitable alternative to fluoroquinolones for treating patients with CAP., (Copyright © 2019. Published by Elsevier B.V.)

The urokinase-type plasminogen activator receptor (uPAR) mediates various cellular activities and is involved in proteolysis, angiogenesis, and inflammation. The objective of this study was to investigate the association between soluble uPAR (suPAR) levels and community-acquired pneumonia (CAP) severity. A commercial enzyme-linked immunosorbent assay (ELISA) was performed to measure the plasma suPAR levels in 67 healthy controls and 75 patients with CAP. Our results revealed that plasma suPAR levels were significantly elevated in patients with CAP compared with the controls, and antibiotic treatment was effective in reducing suPAR levels. The plasma suPAR levels were correlated with the severity of CAP based on the pneumonia severity index (PSI) scores. Furthermore, lipopolysaccharide (LPS)-stimulation significantly increased uPAR expression in RAW 264.7 macrophages. In conclusion, plasma suPAR levels may play a role in the clinical assessment of CAP severity; these findings may provide information on new targets for treatment of CAP., Competing Interests: The authors declare no conflict of interest.

High mobility group box‑1 (HMGB‑1) has been reported to serve significant roles in various inflammatory diseases. However, the correlation between the circulating level of HMGB‑1 and severity of community‑acquired pneumonia (CAP) remains unclear. The present study investigated differential alterations in plasma HMGB‑1 levels of patients with CAP prior to and following antibiotic treatment, and further analyzed the association between CAP severity and HMGB‑1 levels. Furthermore, lipopolysaccharide (LPS)‑induced HMGB‑1 expression in RAW264.7 macrophages and the relevant signaling pathways were examined. Plasma HMGB‑1 levels of 90 patients with CAP and 52 healthy controls were measured using a commercial ELISA. The levels of plasma HMGB‑1 were significantly elevated in CAP patients compared with the controls, and antibiotic treatment was effective in reducing HMGB‑1 levels. Plasma HMGB‑1 correlated with the pneumonia severity index score (r=0.566, P<0.001). Furthermore, LPS‑stimulation significantly upregulated HMGB‑1 secretion via the c‑Jun N‑terminal kinase (JNK) signaling pathway in RAW264.7 macrophages, whereas pretreatment with the JNK inhibitor SP600125 markedly downregulated LPS‑induced HMGB‑1 levels. In conclusion, plasma HMGB‑1 levels may serve a role in the diagnosis and clinical assessment of CAP severity. These findings may provide information on novel targets for the treatment of CAP.

Background: Community-acquired pneumonia (CAP) is characterized as an acute inflammation of the lung associated with the activation of macrophages and neutrophils. Intercellular adhesion molecule-1 (ICAM-1) is an essential adhesion molecule involved in immune cell recruitment in lung inflammation. We investigated whether ICAM-1 is a useful biomarker for assessing the disease severity of hospitalized adult patients with CAP., Methods: Plasma soluble ICAM-1 (sICAM-1) levels were measured in 78 patients with CAP and 69 healthy controls by using a commercial enzyme-linked immunosorbent assay. The pneumonia severity index scores were used to determine CAP severity in patients upon initial hospitalization., Results: The sICAM-1 and C-reactive protein (CRP) levels decreased significantly in patients with CAP after antibiotic treatment. The plasma concentration of sICAM-1 alone, but not CRP, was correlated with CAP severity according to the pneumonia severity index scores (r=0.431, p<0.001). The sICAM-1 levels in patients with CAP with high mortality risk were significantly higher than those in patients with CAP with medium or low mortality risk. Moreover, the sICAM-1 level showed a significant correlation with the length of hospital stay (r=0.488, p<0.001). Mechanistic investigations found that bacterial lipopolysaccharide induced upregulation of ICAM-1 expression through the c-Jun N-terminal kinase pathway in RAW264.7 macrophages., Conclusions: Plasma sICAM-1 levels may play a role in the diagnosis and clinical assessment of CAP severity., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Monocyte chemoattractant protein (MCP)-1 increases in the serum of immunocompetent patients with community-acquired pneumonia (CAP). However, the correlation between the circulating level of MCP-1 and severity of CAP remains unclear. This study investigated differential changes in the plasma MCP-1 levels of patients with CAP before and after an antibiotic treatment and further analyzes the association between the CAP severity and MCP-1 levels. We measured the plasma MCP-1 levels of 137 patients with CAP and 74 healthy controls by using a commercial enzyme-linked immunosorbent assay. Upon initial hospitalization, Acute Physiology and Chronic Health Evaluation II (APACHE II); confusion, urea level, respiratory rate, blood pressure, and age of >64 years (CURB-65); and pneumonia severity index (PSI) scores were determined for assessing the CAP severity in these patients. The antibiotic treatment reduced the number of white blood cells (WBCs) and neutrophils as well as the level of C-reactive protein (CRP) and MCP-1. The plasma MCP-1 level, but not the CRP level or WBC count, correlated with the CAP severity according to the PSI (r = 0.509, p < 0.001), CURB-65 (r = 0.468, p < 0.001), and APACHE II (r = 0.360, p < 0.001) scores. We concluded that MCP-1 levels act in the development of CAP and are involved in the severity of CAP.

Pneumonia is a worldwide infectious disease that is associated with significant morbidity and mortality and is the most common fatal infection acquired in hospitals. Despite advances in preventive strategies, such as antibiotic therapies and intensive care, the mortality rate still requires substantial improvement. Matrix metalloproteinases (MMPs) are a large family of zinc-dependent endopeptidases, which are known as the major enzymes responsible for the proteolytic degradation of proteinaceous components of the extracellular matrix (ECM). Although the main function of MMPs is the removal of the ECM during tissue resorption and progression of various diseases, MMPs also interact with multiple cytokines, participating in the pathology of infection and inflammation. This review presents a schematic overview of the different MMPs expressed in pneumonia. MMPs are key factors in the pathogenesis of various types of pneumonia, such as community-acquired pneumonia, hospital-acquired pneumonia, and ventilator-associated pneumonia. Here, we review the pathological roles of various MMPs in pneumonia., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: The aim of this study was to investigate the differential plasma levels of lipocalin 2 (LCN2) and its complex with MMP-9 (where MMP is matrix metalloproteinase) before and after antibiotic treatment in hospitalized adult patients with community-acquired pneumonia (CAP)., Method: Plasma LCN2 and LCN2/MMP-9 complex levels were measured in 61 adult patients with CAP and 60 healthy controls using commercial enzyme-linked immunosorbent assay (ELISA)., Results: A decrease in the number of white blood cells (WBCs) and neutrophils and decreases in the levels of C-reactive protein (CRP), LCN2, and LCN2/MMP-9 complex were observed after antibiotic treatment. The plasma level of LCN2, but not that of CRP, was correlated with the severity of CAP based on the Pneumonia Severity Index (PSI; r = 0.333, P = 0.009), confusion, urea, respiratory rate and blood pressure (CURB)-65 (r = 0.288, P = 0.024), and Acute Physiology And Chronic Health Evaluation II (APACHE II) scores (r = 0.328, P = 0.010). LCN2 levels were also significantly correlated with LCN2/MMP-9 levels and the numbers of WBCs or neutrophils., Conclusions: Plasma levels of LCN2 and the LCN2/MMP-9 complex can act as adjuvant diagnostic biomarkers for CAP. Plasma LCN2 might play a further role in the clinical assessment of the severity of CAP, which could potentially guide the development of future treatment strategies., (© 2013 Wiley Periodicals, Inc.)

Background: Long pentraxin 3 (PTX3) is an acute-phase protein secreted by various cells, including leukocytes and endothelial cells. Like C-reactive protein (CRP), it belongs to the pentraxin superfamily. The aim of this study was to investigate the differential changes in plasma levels of PTX3 between before and after antibiotic treatment in hospitalized adult patients with community-acquired pneumonia (CAP)., Methods: Plasma PTX3 levels were measured in 61 adult patients with CAP and 60 healthy controls using a commercial enzyme-linked immunosorbent assay (ELISA). Upon initial hospitalization, APACHE II, CURB-65, and pneumonia severity index (PSI) scores were determined to assess CAP severity in patients., Results: The results showed a decline in the number of white blood cells (WBCs) and neutrophils, and decreases in the concentrations of CRP and PTX3 observed after antibiotic treatment. The plasma concentration of PTX3, but not CRP, was correlated with the severity of CAP based on the PSI (r=0.290, p=0.023), CURB-65 (r=0.312, p=0.015), and APACHE II scores (r=0.427, p=0.001). The PTX3 level also exhibited a significant correlation with the length of hospital stay (r=0.500, p<0.0001)., Conclusions: PTX3 may be able to play a role in the diagnosis and clinical assessment of the severity of CAP, which could potentially guide the development of treatment strategies.

Background: We identified the relationship between plasma level changes of cathepsin B and cystatin C before and after antibiotic treatment in hospitalized adult patients with community-acquired pneumonia (CAP)., Methods: We collected blood specimens from 61 adult patients with CAP before and after antibiotic treatment and from 60 healthy controls and measured the plasma concentrations of cathepsin B and cystatin C expression using the enzyme-linked immunosorbent assay (ELISA). The APACHE II, CURB-65, and Pneumonia Severity Index (PSI) scores were determined to assess CAP severity in patients upon initial hospitalization., Results: The results showed a decline in the number of WBCs and neutrophils, with decreases in the concentrations of CRP, cathepsin B, cystatin C, and the cathepsin B/cystatin C ratio being observed after antibiotic treatment. The plasma concentration of cathepsin B correlated with severity of CAP with the PSI score (r=0.290, p=0.025) and the CURB-65 score (r=0.258, p=0.047), respectively. The plasma concentration of cystatin C correlated with the APACHE II score (r=0.523, p<0.001), severity of CAP in the PSI score (r=0.721, p<0.001) and the CURB-65 score (r=0.609, p<0.001), respectively., Conclusions: Cathepsin B and cystatin C may play a role in the diagnosis and clinical assessment of the severity of CAP, which could potentially guide the development of treatment strategies., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: The purpose here was to detect the association among plasma matrix metalloproteinase-9 (MMP-9) concentration, single nucleotide polymorphisms (SNPs) of MMP-9 gene and community-acquired pneumonia (CAP)., Methods: The enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were, respectively used to measure the plasma MMP-9 level and its gene polymorphisms., Results: The level of plasma of MMP-9 was elevated in patients with CAP as compared to that of normal controls and decreased significantly after treatment. Plasma MMP-9 concentration was significantly correlated with white blood cell (WBC) and neutrophil counts in patients with CAP. No significant difference was found in the genotypes distribution of MMP-9 SNPs, rs3918242, rs17576 or rs2274756, between patients with CAP and normal controls. Plasma MMP-9 concentration was not associated with MMP-9 polymorphism. When the cut-off level of the plasma MMP-9 concentration was set to be 105.02 ng/mL, the odds ratio of plasma MMP-9 for CAP risk was 9.86 (95% confident interval: 4.27-22.75). Plasma MMP-9 level may act as a prediction marker for CAP., Conclusions: Elevated plasma MMP-9 could be a biological marker for the diagnosis and be a new strategy for target therapy of community-acquired pneumonia.