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Li Z.-Y.,Key Laboratory of Tropical Diseases and Control of the Ministry of Education | Li Z.-Y.,Sun Yat Sen University | Sun R.,Key Laboratory of Tropical Diseases and Control of the Ministry of Education | Sun R.,Sun Yat Sen University | And 17 more authors.
Journal of Helminthology | Year: 2012

The pathogenesis of angiostrongyliasis, resulting from Angiostrongylus cantonensis invasion of the human central nervous system, remains elusive. Anthelmintics are usually used to kill worms, although dead worms in the brain may cause severe inflammation which will lead to central nervous system damage. Therefore, combination therapy with anthelmintics and anti-inflammatory drugs in the treatment of human angiostrongyliasis needs further study. To evaluate the efficacy of albendazole combined with a marine fungal extract (m2-9) in A. cantonensis infection, BALB/c mice infected by the third-stage larvae of A. cantonensis were divided into three groups: mice treated with albendazole or m2-9 alone or in combination from day 5 post-inoculation (PI). Several efficacy parameters were recorded, including weight change, worm recovery, neurological function, behavioural analysis, eosinophil and leucocyte counts. The results showed that combination therapy increased body weight, reduced worm burden, improved learning ability, memory and action, decreased neurological dysfunction and leucocyte response in these mice. The combination of albendazole and m2-9 treatment significantly decreased leucocyte response and increased the frequency of rearing, compared to infected mice treated with either drug alone. Therefore, m2-9 is a natural product with potentially significant therapeutic value for angiostrongyliasis and is worthy of further study. © 2011 Cambridge University Press.

Chen X.,Key Laboratory of Tropical Diseases and Control of the Ministry of Education | Chen X.,Sun Yat Sen University | Li Z.-Y.,Key Laboratory of Tropical Diseases and Control of the Ministry of Education | Li Z.-Y.,Sun Yat Sen University | And 15 more authors.
Parasitology Research | Year: 2014

Infection with Angiostrongylus cantonensis can cause eosinophilic meningoencephalitis, but it lacks an effective early diagnostic tool for the disease. Recently, growing number of serum microRNAs (miRNAs) were investigated to serve as potentially noninvasive biomarkers for various diseases. However, it is unclear if the molecule can considered a biomarker for diagnosing the infection of A. cantonensis. Here, we attempted to identify potential A. cantonensis-derived miRNAs for the early diagnosis of angiostrongyliasis. Through Solexa deep sequencing and GO "biological process" classifications, we found that there were 18 miRNAs of significantly differential expression in the fourth-stage larvae (L4) larva of A. cantonensis when compared with the third-stage larvae (L3) larva of A. cantonensis. Among the 18 miRNAs, the sequences of 6 miRNAs, including aca-miR-29a, aca-miR-124, aca-miR-125a, aca-miR-146a, aca-miR-101, and aca-miR-185, were different from human- and mouse-derived miRNAs (both are the nonpermissive hosts of A. cantonensis). The expression patterns of the six A. cantonensis-derived miRNAs in serum were investigated by polymerase chain reaction on the A. cantonensis-infected mice and their controls. We found that aca-miR-146a had a significantly higher expression level in every experimental positive group, which suggested that this miRNA might be useful for early diagnosis. Receiver operating characteristic (ROC) curve analysis showed that aca-miR-146a was an effective biomarker for discriminating A. cantonensis-infected mice from healthy control cases, with an area under the ROC curve (AUC) of 0.90. Its diagnostic accuracy was assessed on patients (n = 30) and healthy controls (n = 30), and the sensitivity and specificity reached 83 and 86.7 %, respectively. Our study revealed that aca-mir-146a in serum is an effective biomarker to track infection of A. cantonensis. © 2014 Springer-Verlag Berlin Heidelberg.

Yang J.,Key Laboratory of Tropical Diseases and Control of the Ministry of Education | Yang J.,Sun Yat Sen University | Yang L.,Key Laboratory of Tropical Diseases and Control of the Ministry of Education | Yang L.,Sun Yat Sen University | And 10 more authors.
Parasitology Research | Year: 2012

Schistosoma japonicum is the pathogen responsible for schistosomiasis japonica, one of the major infectious diseases targeted for prevention nationally in China. Expression of heat shock proteins (HSPs) following stress plays a very important biological role in many organisms including S. japonicum. Among the HSP family, the 70-kDa HSPs are most responsible for intracellular chaperone and extracellular immunoregulatory functions. Based on the published sequences in GenBank/EMBL (AF044412.1), open reading frame belonging to HSP70 protein corresponds to a full-length cDNA containing an open reading frame of 1,947 bp encoded of 648 amino acids was identified as HSP70 from schistosome. In this study, the coding region that we named rSj648/hsp70 was amplified from S. japonicum adult worm cDNA library, and the recombinant protein was expressed in vector pET32a(+) and purified using a Ni-NTA purification system. The target protein rSj648/hsp70 was determined by matrixassisted laser desorption/ ionization mass spectrometer after thrombin digestion and dialysis. Reverse transcriptase polymerase chain reaction and Western blotting analysis confirmed that Sj648/hsp70 could be expressed in the eggs, normal cercariae, ultraviolet-attenuated cercariae (UVAC), and adult worms of S. japonicum. Real-time quantitative PCR analysis indicated that Sj648/hsp70 was expressed significantly higher in eggs than that in cercariae and adult worms, and the expression in UVAC was higher than that in normal cercariae. A thermotolerance assay showed that rSj648/hsp70 could protect Escherichia coli cells from heat damage. The detection of specific antibody levels by indirect enzyme-linked immunosorbent assay demonstrated that mice immunized with rSj648/hsp70 induced higher level of specific anti-rSj648/hsp70 IgG1 compared with those vaccinated with adjuvant alone, indicating that rSj648/hsp70 was able to elicit Th2-type bias immune response. Our results suggest that Sj648/hsp70 might be an important molecule in parasite-host interaction and display potential roles in mice immunoregulation system. © Springer-Verlag 2012.

Ning A.,Jiangxi Provincial Institute of Parasitic Diseases | Wu X.,Sun Yat Sen University | Li H.,Jiangxi Provincial Institute of Parasitic Diseases | Liang J.,Key Laboratory of Tropical Diseases and Control of the Ministry of Education | And 16 more authors.
Parasitology Research | Year: 2015

Schistosomiasis japonica, caused by Schistosoma japonicum, is still a serious public health problem in China. It is important for schistosomiasis control to prevent from infection and advanced patients. Recent years, however, the form of the prevalence of schistosomiasis japonica in China was changed these days. Paying attention to the quality of life of these patients already infected with S. japonicum becomes a new objective to schistosomiasis control program. Although most of the chronic infections with S. japonicum will finally appear as liver fibrosis symptoms, it is still unknown liver function abnormalities in patients with severe forms of schistosomiasis, and there is also no evidence whether S. japonicum infection will directly cause damage to liver cells. Thus, this study investigated 494 patients diagnosed with S. japonicum (87.7 %) and 69 healthy subjects from a endemic areas belonging to Jiangxi Province of China and aimed to evaluate the liver function abnormalities in patients with severe forms of schistosomiasis and possible associations with coinfection with HBV. The results showed that the hepatic metabolism situation significantly changed in patients infected with S. japonicum; meanwhile, the abnormal rates of ALT and AST in patients with schistosomiasis were significantly higher than that in the control group, which confirmed that patients infected with S. japonicum not only had damaged liver function but also the hepatic cells were directly influenced. And the coinfection of CHB and schistosomiasis japonica can be a risk factor for more serious outcomes in patients from endemic areas. These results give us the advice that in the further treatment of patients infected with S. japonicum, especially these coinfections, we should better give the routine liver-protection treatment in advance. © 2014, Springer-Verlag Berlin Heidelberg.

Huang F.,Sun Yat Sen University | Huang F.,Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology | Zhang K.,Sun Yat Sen University | Zhang K.,Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology | And 10 more authors.
Clinical Biochemistry | Year: 2013

Objectives: The practical application of elevated carbohydrate antigen 125 (CA125) to predict clinical outcome in chronic heart failure (CHF) is under debate. The mechanism for this CA125 elevation remains unknown. We hypothesize that mechanical stress on mesothelial cells initiates CA125 synthesis. Design and methods: A total of 191 patients suffering from edema and/or dyspnea were enrolled. 109 patients were diagnosed as CHF, and 82 patients without CHF were assigned as control group. Echocardiography, CA125, N-terminal pro-brain natriuretic peptide (NT-proBNP), and other biochemical parameters were measured. All enrolled patients underwent heart function classification. Results: Patients with serous cavity effusion (SCE) demonstrated higher serum CA125 than patients without SCE (82.91 (61.90-103.92) vs. 44.98 (29.66-60.30) U/mL, P. <. 0.001). In the absence of SCE, CA125 levels in CHF patients were slightly higher than non-CHF patients (52.37 (34.85-69.90) vs. 35.15 (23.81-46.49) U/mL, P. = 0.017). Additionally, compared with non-CHF patients, CHF patients had higher levels of high-sensitivity C-reactive protein (hsCRP) and lower superoxide dismutase (SOD). In all enrolled patients, CA125 levels were negatively correlated with SOD concentrations (r. = -. 0.567, P. <. 0.001), and positively correlated with hsCRP levels (r. = 0.608, P. <. 0.001). Receiver operating characteristic curve analysis showed that CA125 was better in predicting SCE than NT-proBNP, while NT-proBNP was more suitable for predicting CHF than CA125. The in vitro study demonstrated that MUC16, the CA125 coding gene, was up-regulated by mechanical stretch on human mesothelial cell line (MeT-5A). Conclusions: CA125 elevation in CHF was associated with SCE. Mechanical extension of mesothelial cells from SCE plays an important role in CA125 increase. © 2013 The Canadian Society of Clinical Chemists.

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