Alantolactone exerts anti-proliferative and apoptotic effects on BGC823 and SGC7901 cells via activation of p38MAPK and inhibition of NF-κB signaling pathway

Purpose: To investigate the anti-proliferative and apoptotic influences of alantolactone on gastric carcinoma (GC) cell lines, and the mechanism(s) involved. Methods: Human gastric cancer cell line (BGC823) and gastric adenocarcinoma lymph node metastasis cell line (SGC7901) were maintained in Ham’s F12 medium supplemented with 10 % heatinactivated fetal bovine serum (FBS). In each group of cancer cell line, 5 groups of cells were used: control and four alantolactone groups which were treated with increasing concentrations of alantolactone (5 - 30 μM) for varying periods. Proliferation was determined using MTT assay, while realtime quantitative polymerase chain reaction (qRT-PCR) was used to assay the expressions of apoptosis- and metastasis-related genes. The expressions of p38MAPK and nuclear transcription factor-κB (NF-κB) in BGC823 and SGC7901 cells were measured with Western blotting. Results: Phosphorylated protein (p-p38 protein) expression was significantly higher in both groups of GC cells, relative to control (p < 0.05). The expressions of NF-κB in plasma protein were markedly higher in both groups of GC cells than in control group, but the corresponding expressions in nuclear protein were significantly lower in both groups of GC cells, relative to control (p < 0.05). Conclusion: Alantolactone exerts anti-proliferative and apoptotic effects on BGC823 and SGC7901 cells via mechanisms involving activation of the p38MAPK, and inhibition of the NF-κB signaling pathways. Thus, alantolactone may be a new and effective anti-gastric cancer drug

San Wu Huangqin Decoction, a Chinese Herbal Formula, Inhibits Influenza a/PR/8/34 (H1N1) Virus Infection In Vitro and In Vivo

The San Wu Huangqin Decoction (SWHD), a traditional Chinese medicine formula, is used to treat colds caused by exposure to wind-pathogen, hyperpyrexia, infectious diseases and cancer; moreover, it is used for detoxification. The individual herbs of SWHD, such as Sophora flavescens and Scutellaria baicalensis, exhibit a wide spectrum of antiviral, anti-inflammatory, antibacterial, anticancer and other properties. The Chinese compound formula of SWHD is composed of S. flavescens, S. baicalensis and Rehmannia glutinosa. However, the effect of SWHD on the influenza virus (IFV) and its mechanism remain unknown. The aim of this study was to evaluate, for the first time, whether SWHD could be used to treat influenza. Results showed that SWHD could effectively inhibit influenza A/PR/8/34 (H1N1) virus at different stages of viral replication (confirmed through antiviral effect assay, penetration assay, attachment assay and internalization assay) in vitro. It could reduce the infection of the virus in a dose- and time-dependent manner, as confirmed by observing the cell cytopathic effect and calculating the cell viability (p < 0.05). SWHD demonstrated better antiviral activity than oseltamivir in the evaluation of antiviral prophylaxis on influenza (p < 0.05). The antiviral activity of SWHD may be related to its regulation ability on the immune system. Western blot, real-time polymerase chain reaction and indirect immunofluorescence assay showed that the expression of the four target viral proteins of the IFV (namely, haemagglutinin (HA), neuraminidase (NA), nucleoprotein (NP) and matrix-2 (M2)) reduced significantly (p < 0.05). Moreover, SWHD (23.40 and 11.70 g/kg) significantly alleviated the clinical signs, reduced the mortality and increased the survival time of infected mice (p < 0.05). The lung index, virus titres, pathological changes in lung tissues and the expression of key proteins of the IFV in mice also decreased (p < 0.05). In conclusion, SWHD possessed anti-influenza activity. This work provided a new view of complementary therapy and drug discovery for clinical treatment

First Report of Two Rapid-Onset Fatal Infections Caused by a Newly Emerging Hypervirulent K. Pneumonia ST86 Strain of serotype K2 in China

Here, we present the first report of one suspected dead case and two confirmed rapid-onset fatal infections caused by a newly emerging hypervirulent Klebsiella pneumoniae ST86 strain of serotype K2. The three cases occurred in a surgery ward during 2013 in Shanghai, China. A combination of multilocus sequence typing, pulsed-field gel electrophoresis, phenotypic and PCR tests for detecting virulence factors (VFs) was used to identify the isolates as K2 ST86 strains with common VFs, including aerobactin and rmpA. Furthermore, the two K2 ST86 strains additionally harbored a distinct VF kfu (responsible for iron uptake system), which commonly existed in invasive K1 strains only. Thus, the unusual presence of both K1 and K2 VFs in the lethal ST86 strain might further enhance its hypervirulence and cause rapid onset of a life-threatening infection. Nevertheless, despite the administration of a combined antibiotic treatment, these three patients all died within 24 hours of acute onset, thereby highlighting that the importance of early diagnosis to determine whether the ST86 strains harbor key K2 VF and unusual K1 kfu and whether patients should receive a timely and targeted antibiotic therapy to prevent ST86 induced fatal pneumonia. Finally, even though these patients are clinically improved, keeping on with oral antibiotic treatment for additional 2-3 weeks will be also vital for successfully preventing hvKP reinfection or relapse