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Li L.,Soochow University of China | Li L.,Key Laboratory on Technology for Parasitic Disease Prevention and Control | Guo Z.,Soochow University of China | Wang J.,Wuxi Infectious Diseases Hospital | And 3 more authors.
Digestive Diseases and Sciences | Year: 2012

Background: Alpha-fetoprotein detection is currently mainly used in clinic for diagnosis of primary hepatocellular carcinoma (HCC). However, its sensitivity and specificity are not satisfying. Approximately 60-80 % of patients with HCC have an established background of chronic infection with hepatitis B virus (HBV). Aims: To investigate the potential of serum microRNAs (miRNAs) as biomarkers for HBV-related HCC. Methods: This study was divided into two phases: firstly, marker (miR-95, miR-18a, miR-10b, miR125a, and miR-378) detection by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) in sera from HBV patients with HCC (n = 15) and health subject (n = 15); and, secondly, marker validation by real-time qRT-PCR on HBV patients with HCC (n = 86) or hepatitis or cirrhosis (n = 30), and healthy subject (n = 45). Results: Serum miR-18a was significantly higher in HBV patients with HCC than healthy controls (p<0.01); serum miR-378 was significantly lower in HBV patients with HCC compared to healthy control (p<0.05). Receiver operating characteristic (ROC) curve analyses suggested that serum miR-18a had significant diagnostic value for HBV-related HCC. MiR-18a yielded an area under the curve (AUC) of ROC of 0.881 with 86.1 % sensitivity and 75.0 % specificity in discriminating HBV-related HCC from healthy controls, and an AUC of ROC of 0.775 with 77.2 % sensitivity and 70.0 % specificity in discriminating HBV-related HCC from chronic hepatitis or cirrhosis. Conclusions: Our results suggest that serum miR-18a might serve as a novel and potential noninvasive biomarker for HBV-related HCC screening. © Springer Science+Business Media, LLC 2012.

Zhang X.-G.,Weifang Medical University | Li G.-X.,Weifang Medical University | Zhao S.-S.,Weifang Medical University | Xu F.-L.,Weifang Medical University | And 3 more authors.
Parasitology Research | Year: 2014

Artemisinin, also known as qinghaosu, is a sesquiterpene lactone endoperoxide extracted from the plant Artemisia annua L, an herb employed in traditional Chinese medicine. Artemisinin and its two main derivatives artemether and artesunate have been shown to be effective against both malaria and schistosomiasis, and therefore, they were described by Liu et al (Parasitol Res 110:2071-2074, 2012b) as the gifts from traditional Chinese medicine not only for malaria control but also for schistosomiasis control. However, another artemisinin derivative dihydroartemisinin (DHA) cannot be neglected. Dihydroartemisinin, a derivative of artemisinin with the C-10 lactone group replaced by hemiacetal and the active metabolite of all artemisinin compounds, was firstly identified as an antimalarial agent, and the dihydroartemisinin- piperaquine combination has been recommended as a first-line treatment of uncomplicated Plasmodium falciparum malaria by the WHO. It has been recently found that administration of dihydroartemisinin at a single dose of 300 mg/kg 2 h or 3, 5, 7, 10, 14, 18, 21, 28, or 35 days post-infection reduces total worm burdens by 1.1-64.8 % and female worm burden reductions by 11.9-90.5 %, and the in vivo activity of dihydroartemisinin against S. japonicum is enhanced by the use of multiple doses. However, a combination of praziquantel and dihydroartemisinin appears no more effective against S. japonicum schistosomulum than treatment with dihydroartemisinin alone. In mice experimentally infected with S. mansoni, administration with dihydroartemisinin at a single dose of 300 mg/kg on days 1, 7, 14, 21, 28, 35, 42, 49, or 56 post-infection results in total worm burden reductions of 13.8-82.1 % and female worm burden reductions of 13-82.8 %, and a clear-cut dose-response relationship of dihydroartemisinin against the schistosomula and adult worms of S. mansoni is observed. In addition, dihydroartemisinin was found to cause damages to the reproductive system of female S. mansoni worms, reduce the oviposition of survival worms, and inhibit the formation of granulomas around tissue-trapped eggs. More interestingly, no reduced sensitivity to dihydroartemisinin is detected in praziquantel non-susceptible S. japonicum, which provides a new option for the treatment of S. japonicum and S. mansoni infections, notably in endemic foci with praziquantel resistance or insensitivity detected. It is therefore considered that dihydroartemisinin is another gift from the traditional Chinese medicine not only for malaria control but also for schistosomiasis control. © 2014 Springer-Verlag.

Li H.-J.,Weifang Medical University | Xu F.-L.,Weifang Medical University | Wang Y.-H.,Weifang Medical University | Yi Z.-J.,Weifang Medical University | And 2 more authors.
Parasitology Research | Year: 2014

Currently, praziquantel is the drug of choice for the treatment of human Schistosoma mansoni infections. It has not been proved until now that there is real praziquantel resistance, but there is decreased praziquantel sensitivity. A search for novel antischistosomal agents against the parasite has been given a high priority. Dihydroartemisinin, formerly identified as an antimalarial drug, has been shown to be active against both Schistosoma japonicum and S. mansoni in mice. Interestingly, dihydroartemisinin is found to be highly effective against the 14-28-day schistosomula of S. mansoni, and treatment with multiple low doses of the drug achieves a high efficacy with reduced toxicity to the host. The long time development from juveniles to adults allows adequate timing for treatment of this neglected tropical disease. It is supposed that dihydroartemisinin, a safe orally administered agent, may be used for the prevention and control of human S. mansoni infections, notably in areas with reduced praziquantel sensitivity or praziquantel resistance detected. © 2013 Springer-Verlag Berlin Heidelberg.

Liu Q.,Soochow University of China | Tao Y.-H.,Key Laboratory on Technology for Parasitic Disease Prevention and Control | Bai R.-Z.,Soochow University of China | Chang S.-J.,Soochow University of China | Hua D.,Soochow University of China
Chinese Medical Journal | Year: 2013

Background Growing preclinical evidence shows that zoledronic acid (ZOL) exhibits direct antitumor activity in various cancer cell lines. However, the cytotoxic effects of ZOL on human hepatocellular carcinoma (HCC) cells have not been established. In the present study, we investigated the effect of ZOL on HCC both in vitro and in vivo. Methods Cytotoxicity and cell cycles were assessed with Sulforhodamine B colorimetric assay and flow cytometry. Expression levels of cell cycle phase-linked proteins were examined. The effect of ZOL on HCC in vivo was explored based on H22-subcutaneous injection (s.c.) and H22-intraperitoneal injection (i.p.) mice model. Results ZOL inhibited the growth of SK-HEP-1 and H22 cells and induced S-phase arrest through downregulating cdc2 protein and upregulating cyclin A. It inhibited the growth of s.c tumors, and increased the survival of both H22-s.c. and H22-i.p. mice in vivo. Conclusion ZOL inhibits growth of HCC cells in vitro and in vivo.

Zhou L.-Y.,Jiangnan University | Deng Y.,Jiangsu Institute of Parasitic Diseases | Steinmann P.,Swiss Tropical and Public Health Institute | Steinmann P.,University of Basel | And 2 more authors.
Parasitology International | Year: 2013

Schistosomiasis japonica continues to be an important zoonotic disease in the People's Republic of China (P.R. China), despite decades of dedicated control efforts. Different interventions for its control including chemotherapy of humans and animals, mollusciciding, environmental modification, and health education have been implemented at various stages of the control efforts and in different combinations, resulting in remarkable achievements. Here, we present a systematic review and meta-analysis of the documented effectiveness of health education to reduce schistosomiasis japonica transmission in P.R. China. A total of 10 relevant publications were identified and included in the meta-analysis. The reported results indicate that the prevalence of Schistosoma japonicum infection in humans and schistosomiasis-related knowledge are significantly influenced by health education. The implementation of health education over more than 2. years was associated with an overall schistosomiasis japonica prevalence decrease of 6% (95% CI: 2%, 11%) and an overall increase of 51% (95% CI: 41%, 61%) in schistosomiasis-related knowledge after controlling for confounding factors. Among control groups, the prevalence of schistosomiasis japonica and relevant knowledge levels were not significantly influenced. The relative risk (RR) of an infection with S. japonicum following health education lasting more than 2. years was 0.43 (95% CI: 0.24, 0.78). In summary, a considerable effectiveness of health education with regard to preventing S. japonicum infections in P.R. China and increasing relevant knowledge is documented in the extant literature. This suggests that the effectiveness of health education may be considerable, particularly after its long-term implementation. © 2012 Elsevier Ireland Ltd.

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