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This study aimed to investigate the prevalence of multidrug-resistant tuberculosis (MDR-TB) isolates resistant to the second-line antituberculosis drugs (SLDs) and its association with resistant-related gene mutations in Mycobacterium tuberculosis (M.tb) isolates from Southwest of China. There were 81 isolates resistant to at least one of the SLDs among 156 MDR-TB isolates (81/156, 51.9%). The rates of general resistance to each of the drugs were as follows: OFX (66/156, 42.3%), KAN (26/156, 16.7%), CAP (13/156, 8.3%), PTO (11/156, 7.1%), PAS (22/156, 14.1%), and AMK (20/156, 12.8%). Therefore, the most predominant pattern was resistant to OFX compared with other SLDs (P<0.001). The results of sequencing showed that 80.2% OFX-resistant MDR-TB isolates contained gyrA mutation and 88.5% KAN-resistant isolates had rrs mutations with the most frequent mutation being A1401G. These results suggest that improper use of SLDs especially OFX is a real threat to effective MDR-TB treatment not only in China but also in the whole world. Furthermore the tuberculosis control agencies should carry out SLDs susceptibility testing and rapid screening in a broader population of TB patients immediately and the SLDs should be strictly regulated by the administration in order to maintain their efficacy to treat MDR-TB. [ABSTRACT FROM AUTHOR]

Aim 15-Lipoxygenase (15-LO) is an important factor in the pathogenesis of pulmonary artery hypertension (PAH). However, the role of 15-LO in the adventitia of the pulmonary arterial wall is unclear. The aim of this study was to explore the role of 15-LO in the modulation of pulmonary adventitial fibroblast (PAF) dynamics. Methods Rats were exposed to normoxic or hypoxic (fraction of inspired O2 = 0.12) treatments for 7 days. PAF proliferation and cell cycle alterations were measured by MTT assay, cell immunofluorescence, flow cytometry and Western blot analysis. The 15-LO promoter was analysed by luciferase reporter and ChIP assays. Results Our results showed that hypoxia induced 15-LO expression in PAFs both in vivo and in vitro. In addition, hypoxia stimulated JNK phosphorylation in PAFs. Blocking 15-LO or JNK suppressed 15-LO-induced PAF proliferation and cell cycle alterations. The inhibition of p27kipl by gene silencing attenuated 15-LO-induced PAF proliferation and cell cycle alterations. Furthermore, JNK inhibition or Elk-1 knockdown suppressed hypoxia-induced 15-LO expression in PAFs. Luciferase reporter and ChIP assays revealed that the 15-LO promoter contains Elk-1-binding sites and also that Elk-1 increased the hypoxia-induced activity of the 15-LO promoter. Conclusion These results suggest that hypoxia promotes changes in the cellular dynamics of PAFs by inducing 15-LO expression, which leads to vascular adventitial remodelling. The modulation of p27kipl expression by 15-LO enhances PAF proliferation and cell cycle alterations. Furthermore, the JNK-dependent increase in Elk-1 signalling is required for hypoxia-induced 15-LO expression in PAFs. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the genetic characteristics of fluoroquinolone-nonsusceptible Streptococcus pneumoniae clinical isolates in China. A total of 377 S. pneumoniae clinical isolates, including 307 pediatric strains and 70 adult strains, were collected from eight centers in China. The minimal inhibitory concentrations (MICs) of 10 antimicrobial agents were determined by agar dilution. Multilocus sequence typing (MLST), serotyping, and quinolone resistance-determining region (QRDR) variations were conducted in levofloxacin-nonsusceptible isolates by polymerase chain reaction (PCR)-based methods. Seven levofloxacin-nonsusceptible isolates were found, with an overall resistance rate of 1.9 % (7/377) and 8.6 % (6/70) in adults. Sequence analyses of parC, gyrA, and parE QRDRs in levofloxacin-resistant isolates demonstrated mutations in dual target sites at the hot spots. These seven strains represented multiple clones: two strains were serotype 19F (Taiwan-14) and MLST clonal complex (CC) 271/320, two were typed as 23F (Spain-1) and CC81, two were determined as serotype 20B and a new sequence type of ST6935, and one non-serotypeable pediatric strain belonged to a new sequence type of ST6946. Two serotype 19F strains possessed a variety of characteristic alterations of viridans group streptococci in gyrA (Ser114Gly) or parC (Ser52Gly, Asn91Asp). Fluoroquinolone-nonsusceptible S. pneumoniae isolates showed a substantial degree of genetic diversity and belonged to pre-existing epidemic clones together with native clones. S. pneumoniae strains with serotype 20B was recovered for the first time to be associated with levofloxacin resistance in China. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate whether hemoglobin-based oxygen carrier (HBOC) could protect the heart from intense exercise-induced myocardial dysfunction. Adult male Sprague-Dawley rats were subjected to 5-h intense prolonged running on treadmill with or without HBOC pre-treatment. Immediately after exercise, the heart rate (HR) and oxygen delivery capacity of the blood were measured. After 1 h of rest, echocardiography was performed to assess the post-exercise cardiac function. Then all the hearts were isolated and perfused using the Langendorff model for 1 h. Our results proved that pronged exercise caused significant LV dysfunction, while HBOC pre-treatment attenuated such a damage, as evidenced by the increased oxygen delivery, cardiac fractional shortening (FS), rate-pressure product (RPP), ± dp/dt and coronary flow rate (CF) and decreased myocardial necrosis. The releases of cardiac enzymes, including creatine kinase-MB (CK-MB) and cardiac troponin-I (cTnI) were markedly reduced. No significant difference of cardiac infarct size was observed among groups. In addition, HBOC significantly elevated superoxide dismutase (SOD) activity and decreased hydrogen peroxide (H2O2) formation, which indicated the exercise-induced cardiac oxidative damage was inhibited. In conclusion, HBOC pre-treatment showed a promising cardioprotective effect on prolonged exercise-induced cardiac dysfunction, which was probably associated with its ability to decrease myocardium oxidative stress. [ABSTRACT FROM AUTHOR]

We previously showed that human amnion epithelial cells (hAECs) are a viable source of cell therapy for established bronchopulmonary dysplasia (BPD). This work has culminated in a first-in-human clinical trial in babies with established BPD. In this current study, we sought to assess the therapeutic potential of hAEC-derived EVs (hAEC-EVs) in an experimental model of BPD. Lipopolysaccharide (LPS) was introduced to C57bl6 mouse fetuses intra-amniotically at E16 prior to exposure to 65% oxygen (hyperoxia) at birth. hAEC-EVs were injected intravenously on postnatal day (PND) 4. One cohort of mice were culled on either postnatal day PND7 or PND14, while another cohort were kept in hyperoxia until PND 28, following which they were recovered under normoxia conditions for a further 2 weeks or 6 weeks for cardiovascular assessment. The isolated hAEC-EVs had distinct cup shaped morphology with average size of 80-140nm. ALIX, Grp94 and HLA-G were expressed in EVs, and Pathway enrichment analysis showed that endothelin signaling pathway, Wnt signaling pathway, and inflammation mediated by chemokine and cytokine signaling pathway were enriched in hAEC-EVs. In the mouse model of experimental BPD, hAEC-EV administration improved tissue-to-airspace ratio and septal crest density in a dose-dependent manner. hAEC-EVs reduced the levels of inflammatory cytokines such as interleukin (IL)-1β and tumour necrosis factor-alpha (TNF-α) on PND7. The improvement of lung injury was associated with the increase of the percentage of type II alveolar cells (AT2s) at both PND7 and 14. Surprisingly, neonatal hAEC-EV delivery reduced airway hyper-responsiveness, mitigated pulmonary hypertension and prevented right ventricle hypertrophy that associated with BPD-like lung injury at week 6. These improvements persisted till week 10. All these observations showed that HAEC-EVs mitigate the BPD lung injury through decreasing inflammation, activating local AT2 niche and reversing pulmonary artery remodeling. hAEC-derived EVs had similar therapeutic effects to hAECs in this mouse model of experimental BPD. hAEC-derived EVs improved lung structure and reduced lung inflammation in a manner similar to that achieved using hAECs. EVs repaired lung injury partly through the activation of local stem/progenitor cells. Furthermore, hAEC-EV administration had long term benefit in improving lung function, preventing pulmonary hypertension and right ventricle hypertrophy. [ABSTRACT FROM AUTHOR]

To assess the immunogenicity of an inactivated new type gosling viral enteritis virus (NGVEV) vaccine, we investigated 3 different doses of the inactivated vaccine and the inactivated vaccine in conjunction with 3 different doses of recombinant goose interleukin-2 (rGoIL-2) adjuvant. A virus concentration of 105 50% embryo infective dose/mL was subcutaneously inoculated into adult geese divided into 6 groups. The dynamic changes of the humoral and cellular immunity responses elicited by the vaccines in the adult geese postvaccination (PV) were investigated using ELISA, virus neutralization test, and lymphocyte proliferation assay. The clearance of virus from the intestines of geese (175 d PV) was studied by histopathological examination and indirect immunofluorescence assay after virulent NGVEV challenge. This study showed that the inactivated NGVEV vaccine elicits strong humoral and cellular responses in the vaccinated adult geese. The absorbance values of specific anti-NGVEV anti-bodies, the neutralization antibody titer, and the lymphocyte proliferation index rapidly increased, peaked at about 28 d PV, progressed to the plateau stage, and then decreased slightly. The rGoIL-2 adjuvant enhanced the immune response, and this adjuvant in conjunction with the inactivated NGVEV vaccine induces a significantly higher specific anti-NGVEV antibody absorbance value, neutralization antibody titer, and lymphocyte proliferation index than the non-adjuvantinactivated NGVEV vaccine (P < 0.05). The inactivated NGVEV vaccine conferred adequate efficient ability to clear NGVEV in vaccinated geese even in the last phase of the vaccination period (175 d PV). The inactivated NGVEV vaccine (0.5 mL/goose) with 1,000 units of rGoIL-2 adjuvant/goose is the most effective dose, thereby eliciting the strongest humoral and cellular immunity responses and providing the most efficacious clearance of NGVEV in vivo. [ABSTRACT FROM AUTHOR]