Mycoplasma genitalium Lipoproteins Induce Human Monocytic Cell Expression of Proinflammatory Cytokines and Apoptosis by Activating Nuclear Factor κB

This study was designed to investigate the molecular mechanisms responsible for the induction of proinflammatory cytokines gene expression and apoptosis in human monocytic cell line THP-1 stimulated by lipoproteins (LPs) prepared from Mycoplasma genitalium. Cultured cells were stimulated with M. genitalium LP to analyze the production of proinflammatory cytokines and expression of their mRNA by ELISA and RT-PCR, respectively. Cell apoptosis was also detected by Annexin V-FITC-propidium iodide (PI) staining and acridine orange (AO)-ethidium bromide (EB) staining. The DNA-binding activity of nuclear factor-κB (NF-κB) was assessed by electrophoretic mobility shift assay (EMSA). Results showed that LP stimulated THP-1 cells to produce tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 in a dose-dependent manner. The mRNA levels were also upregulated in response to LP stimulation. LPs were also found to increase the DNA-binding activity of NF-κB, a possible mechanism for the induction of cytokine mRNA expression and the cell apoptosis. These effects were abrogated by PDTC, an inhibitor of NF-κB. Our results indicate that M. genitalium-derived LP may be an important etiological factor of certain diseases due to the ability of LP to produce proinflammatory cytokines and induction of apoptosis, which is probably mediated through the activation of NF-κB

Prognostic Value of Gamma-Glutamyl Transpeptidase to Lymphocyte Count Ratio in Patients With Single Tumor Size ≤ 5 cm Hepatocellular Carcinoma After Radical Resection

Prediction of prognosis of hepatocellular carcinoma (HCC) has shown an important role in improving treatment outcomes and preventing disease progression, however, the prognostic indicator of HCC is still lacking. The purpose of this study is to investigate the predictive value of GLR (gamma-glutamyl transpeptidase to lymphocyte count ratio) in single HCC with a tumor size (TS) ≤ 5 cm. A retrospective analysis was performed on 272 patients with TS ≤ 5 cm who underwent radical resection. The Pearson χ2 test was applied to discuss the relationship between HCC and GLR, alpha-fetoprotein (AFP). Then univariate and multivariate analysis was utilized to predict the risk factors for survival prognosis in patients. In this study, GLR showed a positive relation with tumor size, tumor-node-metastasis (TNM) stage, microvascular invasion, early recurrence, and serum aspartate aminotransferase (AST) level, while the AFP value only correlated with drinking. Elevated GLR value had poor overall survival (OS) and progression-free survival (PFS) of TS ≤ 5 cm HCC patients, GLR level and tumor size were closely related to the prognosis of small HCC patients compared with AFP. GLR may serve as a prognostic marker for dynamic monitoring of HCC patients with single TS ≤ 5 cm after radical resection

Morphology-related foot function analysis:implications for jumping and running

Barefoot and shod running has received increased attention in recent years, however, the influence of morphology-related foot function has not been explored. This study aimed to investigate morphology-related jumping and running biomechanical functions in habitually barefoot and shod males. A total of 90 barefoot males (Indians) and 130 shod males (Chinese), with significant forefoot and toe morphology differences, participated in a vertical jump and running test to enable the collection of kinematic and kinetic data. The difference of pressure distribution in the hallux and forefoot was shown while jumping and running. The unrestricted forefoot and toes of the barefoot group presented flexible movement and leverage functions to expand the forefoot loading area during performance of the two tasks. Findings related to morphology functions, especially in the forefoot and toe may provide useful information for footwear design

ZYZ-168 alleviates cardiac fibrosis after myocardial infarction through inhibition of ERK1/2-dependent ROCK1 activation

Selective treatments for myocardial infarction (MI) induced cardiac fibrosis are lacking. In this study, we focus on the therapeutic potential of a synthetic cardio-protective agent named ZYZ-168 towards MI-induced cardiac fibrosis and try to reveal the underlying mechanism. ZYZ-168 was administered to rats with coronary artery ligation over a period of six weeks. Ecocardiography and Masson staining showed that ZYZ-168 substantially improved cardiac function and reduced interstitial fibrosis. The expression of α–smooth muscle actin (α-SMA) and Collagen I were reduced as was the activity of matrix metalloproteinase 9 (MMP-9). These were related with decreased phosphorylation of ERK1/2 and expression of Rho-associated coiled-coil containing protein kinase 1 (ROCK1). In cardiac fibroblasts stimulated with TGF-β1, phenotypic switches of cardiac fibroblasts to myofibroblasts were observed. Inhibition of ERK1/2 phosphorylation or knockdown of ROCK1 expectedly reduced TGF-β1 induced fibrotic responses. ZYZ-168 appeared to inhibit the fibrotic responses in a concentration dependent manner, in part via a decrease in ROCK 1 expression through inhibition of the phosphorylation status of ERK1/2. For inhibition of ERK1/2 phosphorylation with a specific inhibitor reduced the activation of ROCK1. Considering its anti-apoptosis activity in MI, ZYZ-168 may be a potential drug candidate for treatment of MI-induced cardiac fibrosis

Causative agent distribution and antibiotic therapy assessment among adult patients with community acquired pneumonia in Chinese urban population

<p>Abstract</p> <p>Background</p> <p>Knowledge of predominant microbial patterns in community-acquired pneumonia (CAP) constitutes the basis for initial decisions about empirical antimicrobial treatment, so a prospective study was performed during 2003–2004 among CAP of adult Chinese urban populations.</p> <p>Methods</p> <p>Qualified patients were enrolled and screened for bacterial, atypical, and viral pathogens by sputum and/or blood culturing, and by antibody seroconversion test. Antibiotic treatment and patient outcome were also assessed.</p> <p>Results</p> <p>Non-viral pathogens were found in 324/610 (53.1%) patients among whom <it>M. pneumoniae </it>was the most prevalent (126/610, 20.7%). Atypical pathogens were identified in 62/195 (31.8%) patients carrying bacterial pathogens. Respiratory viruses were identified in 35 (19%) of 184 randomly selected patients with adenovirus being the most common (16/184, 8.7%). The nonsusceptibility of <it>S. pneumoniae </it>to penicillin and azithromycin was 22.2% (Resistance (R): 3.2%, Intermediate (I): 19.0%) and 79.4% (R: 79.4%, I: 0%), respectively. Of patients (312) from whom causative pathogens were identified and antibiotic treatments were recorded, clinical cure rate with β-lactam antibiotics alone and with combination of a β-lactam plus a macrolide or with fluoroquinolones was 63.7% (79/124) and 67%(126/188), respectively. For patients having mixed <it>M. pneumoniae </it>and/or <it>C. pneumoniae </it>infections, a better cure rate was observed with regimens that are active against atypical pathogens (e.g. a β-lactam plus a macrolide, or a fluoroquinolone) than with β-lactam alone (75.8% vs. 42.9%, <it>p </it>= 0.045).</p> <p>Conclusion</p> <p>In Chinese adult CAP patients, <it>M. pneumoniae </it>was the most prevalent with mixed infections containing atypical pathogens being frequently observed. With <it>S. pneumoniae</it>, the prevalence of macrolide resistance was high and penicillin resistance low compared with data reported in other regions.</p