Key Laboratory of Tropical Disease Control

Guangzhou, China

Key Laboratory of Tropical Disease Control

Guangzhou, China
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He P.,Sun Yat Sen University | He P.,Key Laboratory of Tropical Disease Control | He P.,Minzu University of China | Wang W.,National Institute of Parasitic Diseases | And 14 more authors.
Parasites and Vectors | Year: 2017

Background: Schistosomiasis mansoni is one of the most important, but often neglected, tropical diseases transmitted by snails of the genus Biomphalaria. Control of the intermediate host snail plays a crucial role in preventing the spread of schistosomiasis. However, there is only one molluscicide, niclosamide, recommended by the World Health Organization. Niclosamide has been used for several decades but is toxic to non-target organisms. Therefore, it is necessary to optimize the scaffold of niclosamide and develop novel molluscicides with enhanced potency and decreased toxicity to non-target organisms. Methods: In this study, a candidate compound was analyzed by nuclear magnetic resonance and mass spectrometry. The molluscicidal potential against Biomphalaria species and cercaricidal potential against S. mansoni were evaluated using the immersion method. Furthermore, the preliminary mechanism was studied through cellular enzyme tests and electron microscopy. Results: 5-chloro-2-[(2-chloro-4-nitrophenyl)carbamoyl]phenyl-4-methoxybenzoate (salicylanilidate), a novel salicylanilide ester derivative, was derived from niclosamide. The 50% lethal concentration to B. glabrata, B. straminea and B. pfeifferi was 0.261 mg/l, 0.172 mg/l and 0.241 mg/l, respectively. The effective dose required to completely kill S. mansoni cercariae was 0.625 mg/l for salicylanilidate and 0.125 mg/l for niclosamide. However, salicylanilidate was approximately 100-fold less toxic to the fish Danio rerio than niclosamide. Furthermore, salicylanilidate reduced the enzymatic activities of nitric oxide synthase (NOS), lactate dehydrogenase (LDH) and acetylcholinesterase (AChE) in the snail, demonstrating that it could affect neurohypophysis transmission and energy metabolism. Severe swelling in the tentacle and deformation of cilia in the tentacle and mantle were observed through scanning electron microscopy. The results of transmission electron microscopy showed that salicylanilidate could damage critical organelles in hepatopancreas tissues, including degeneration of the endoplasmic reticulum and vacuolization in mitochondria. In addition, transcriptional levels of superoxide dismutase (SOD), acid phosphatase (ACP) and NOS in the hepatopancreas were significantly downregulated as shown by real-time quantitative polymerase chain reaction (RT-PCR). These results indicated that the hepatopancreas is a primary target organ of salicylanilidate. Conclusions: Salicylanilidate not only had deleterious effects on Biomphalaria species and S. mansoni cercariae but also showed very low toxicity to D. rerio, suggesting that it has broad potential applications. © 2017 The Author(s).

Zhang Z.J.,Sun Yat Sen University | Xia Y.,Sun Yat Sen University | Lu Y.,Southern Medical University | Yang J.C.,Key Laboratory of Tropical Disease Control | And 8 more authors.
Chinese Medical Journal | Year: 2014

Background In March 2013, human cases of infection with a novel A (H7N9) influenza virus emerged in China. The epidemic spread quickly and as of 6 May 2013, there were 129 confirmed cases. The purpose of this study was to analyze the epidemiology of the confirmed cases, determine the impacts of bird migration and temperature changes on the H7N9 epidemic, predict the future trends of the epidemic, explore the response patterns of the government and propose preventive suggestions. Methods The geographic, temporal and population distribution of all cases reported up to 6 May 2013 were described from available records. Risk assessment standard was established by analysing the temperature and relative humidity records during the period of extensive outbreak in three epidemic regions in eastern China, including Shanghai, Zhejiang and Jiangsu provinces. Risk assessment maps were created by combining the bird migration routes in eastern China with the monthly average temperatures from May 1993 to December 2012 nationwide. Results Among the confirmed cases, there were more men than women, and 50.4% were elderly adults (age >61 years). The major demographic groups were retirees and farmers. The temperature on the days of disease onset was concentrated in the range of 9°C-19°C; we defined 9°C-19°C as the high-risk temperature range, 0°C-9°C or 19°C-25°C as medium risk and <0°C or >25°C as low risk. The relative humidity on the days of disease onset ranged widely from 25% to 99%, but did not correlate with the incidence of infection. Based on the temperature analysis and the eastern bird migration routes, we predicted that after May, the high-risk region would move to the northeast and inland, while after September, it would move back to north China. Conclusions Temperature and bird migration strongly influence the spread of the H7N9 virus. In order to control the H7N9 epidemic effectively, Chinese authorities should strengthen the surveillance of migrating birds, increase poultry and environmental sampling, improve live poultry selling and husbandry patterns and move from a "passive response pattern" to an "active response pattern" in focused preventive measures.

Xu B.,Institute of Human Virology | Xu B.,Key Laboratory of Tropical Disease Control | Wang L.,Sun Yat Sen University | Gonzalez-Molleda L.,University of Pennsylvania | And 6 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2014

Kaposi's sarcoma-associated herpesvirus (KSHV) is an etiological agent of several AIDS-associated malignancies, including Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD). Its lytic replication cycle has been proven to be critical for the pathogenesis of KSHV-associated diseases. In KS lesions, lytic viral replication, production of virion particles, and reinfection of endothelial cells are essential to sustain the population of infected cells that otherwise would be quickly lost as spindle cells divide. Thus, antivirals that block KSHV replication could be a strategy in the treatment of KSHV-associated diseases. However, there is no effective anti-KSHV drug currently available. Our previous work showed that human topoisomerase II (Topo II) is indispensable for KSHV lytic replication and is suggested to be an effective target for antiviraldrugs. Here, we report the discovery and characterization of a novel catalytic inhibitor of human Topo IIα, namely, (+)-rutamarin.The binding mode of (+)-rutamarin to the ATPase domain of human Topo IIα was established by docking and validated by molecular dynamics (MD) simulations. More importantly, (+)-rutamarin efficiently inhibits KSHV lytic DNA replication in BCBL-1 cells with a half-maximal inhibitory concentration (IC50) of 1.12 μMand blocks virion production with a half-maximal antiviral effective concentration (EC 50) of 1.62 μM. It possesses low cytotoxicity, as indicated by the selectivity index (SI) of 84.14. This study demonstrated great potential for (+)-rutamarin to become an effective drug for treatment of human diseases associated with KSHV infection. © 2014, American Society for Microbiology. All Rights Reserved.

Wei J.,Sun Yat Sen University | Wei J.,Key Laboratory of Tropical Disease Control | Wu F.,Sun Yat Sen University | Wu F.,Key Laboratory of Tropical Disease Control | And 13 more authors.
Parasitology Research | Year: 2013

Angiostrongylus cantonensis is a rodent nematode. Adult worms of A. cantonensis live in the pulmonary arteries of rats. Humans and mice are accidental hosts or named nonpermissive hosts. The larva cannot develop into an adult worm and only causes serious eosinophilic meningitis or meningoencephalitis if humans or mice eat food containing larva of A. cantonensis in the third stage. The differing consequences largely depend on differing immune responses of the host to parasite during A. cantonensis invasion and development. Microglia is considered to be the key immune cell in the central nervous system like macrophage. To further understand the reasons for why mice and rats attain different outcomes in A. cantonensis infection, we set up the method to isolate and culture newborn rats' primary microglia and observe the activation of the microglia cells, comparing with mice microglia cell line N9. We treated cells with soluble antigen of the fourth larva of A. cantonensis (L4 larva) and measured mRNA levels of IL-1β, IL-5, IL-6, IL-13, eotaxin, iNOS, and TNF-α by real-time PCR. The results showed that N9 expressed high mRNA level of IL-6, IL-1β, TNF-α, iNOS, IL-5, IL-13, and eotaxin, but primary microglia only had IL-5, IL-13, and eotaxin mRNA level. It implies that microglia from rats and mice had different reaction to soluble antigen of A. cantonensis. Therefore, we supposed that microglia may play an immune modulation role during the brain inflammation induced by A. cantonensis. © 2012 Springer-Verlag Berlin Heidelberg.

Li Z.-T.,Sun Yat Sen University | Zhang R.-L.,Sun Yat Sen University | Bi X.-G.,Sun Yat Sen University | Xu L.,Sun Yat Sen University | And 9 more authors.
Microbial Pathogenesis | Year: 2015

Outer membrane vesicles (OMVs) are well-characterized virulence factors produced by Gram-negative bacteria. Here, we isolated two clinical Acinetobacter baumannii strains, the multidrug-resistant A.baumannii (MDRAb) A38 and non-MDRAb 5806. Strain A38 produced more abundant OMVs than strain 5806 when cultured to the early stationary phase. The results from cell proliferation assays and real-time PCR analyses indicated that A38 OMVs induced more powerful cytotoxicity and stronger innate immune responses compared with 5806 OMVs. Moreover, SDS-PAGE and LC-MS/MS analyses revealed that A38 OMVs contained more virulence factors, including Omp38, EpsA, Ptk, GroEL, hemagglutinin-like protein, and FilF. Taken together, the results of the present study suggest that MDRAb might produce abundant OMVs with more virulent factors facilitating the worse outcome, a finding that merits further study. © 2015 Elsevier Ltd.

Song L.,Sun Yat Sen University | Song L.,Key Laboratory of Tropical Disease Control | Wang X.,Sun Yat Sen University | Yang Z.,Sun Yat Sen University | And 4 more authors.
Parasitology Research | Year: 2015

Angiostrongyliasis is a food-borne parasitic disease induced by the nematode Angiostrongylus cantonensis, and has been recognized as the main cause leading to human eosinophilic meningitis. Humans usually acquire infection by digestion of infected Pomacea canaliculata and Achatina fulica, the most predominant intermediate hosts found in China. This meta-analysis was aimed to assess the prevalence of A. cantonensis infection among these two snails in China in the past 10 years. Data were systematically collected in electronic databases such as PubMed, Web of Science, ScienceDirect, CNKI, SinoMed, VIP, CSCD, and Wanfang from 2005 to 2015. Thirty-eight studies with a total of 41,299 P. canaliculata and 21,138 Ac. fulica were included in the present study. The overall infection rate of A. cantonensis in China was estimated to be 7.6 % (95 % confidential interval (CI) = 0.063 to 0.090) in P. canaliculata and 21.5 % in Ac. fulica (95 % CI = 0.184 to 0.245), respectively. No significant difference was observed in prevalence rates among publication year and sample size for both snails. Also, it was found that the prevalence in Ac. fulica is significantly higher than that in P. canaliculata (odds ratio (OR) = 3.946, 95 % CI = 3.070 to 5.073). The present study reveals that snail infection with A. cantonensis is clearly prevalent in China. Further studies are required to improve strategies for control of infections of snails, particularly those of Ac. fulica, and to detect further factors and conditions such as geographic region, temperatures, and diagnosis method. © 2015 Springer-Verlag Berlin Heidelberg

Yang F.,Sun Yat Sen University | Yang F.,Key Laboratory of Tropical Disease Control | Sun X.,Sun Yat Sen University | Sun X.,Key Laboratory of Tropical Disease Control | And 10 more authors.
Parasitology Research | Year: 2013

rSj16, a recombined protein from Schistosoma japonicum, has been identified as an anti-inflammatory molecule. In this study, we demonstrated that rSj16 strongly suppressed the growth of murine myeloid leukemia WEHI-3B JCS cells in a dose- and time-dependent manner. rSj16 induced apoptosis by increasing the proportion of sub-G1 apoptotic cells as well as causing cell cycle arrest at the G0/G1 phase. The expressions of cyclin D1, D2, D3, and E, and Cdk 2, 4, and 6 genes in WEHI-3B JCS cells were significantly down-regulated at 24 h as measured by real-time PCR. Furthermore, apoptosis induced by rSj16 was confirmed by 4,6-diamidino-2-phenylindole nuclear staining assay and annexin V/propidium iodide double staining. A reduction of the mitochondrial membrane potential indicated an active involvement of mitochondria in the apoptosis process. rSj16 treatment induced an increase in the activity of caspase 3, 6, and 9, and expression of pro-apoptotic Bax. Meanwhile, the decreased expression of anti-apoptotic Bcl-2 was observed after rSj16 treatment. Taken together, our results implied that rSj16 can inhibit proliferation by inducing G0/G1 cell cycle arrest and apoptosis of murine myeloid leukemia cells via activation of the caspase-mediated mechanism by regulating the expression of Bcl-2 family. © 2012 Springer-Verlag Berlin Heidelberg.

Yu M.,Sun Yat Sen University | Yu M.,Key Laboratory of Assisted Circulation | Lu G.,Sun Yat Sen University | Lu G.,Key Laboratory of Assisted Circulation | And 7 more authors.
Molecular Medicine Reports | Year: 2016

High glucose-induced endothelial cell apoptosis is considered to be the initiator of diabetes-associated vascular complications. Experiments in vivo and in vitro have demonstrated that high glucose levels contribute to the apoptosis of endothelial cells by mediating cellular dysfunction and metabolic disorder via the production of various cytokines. As the most important endogenous vascular regulators, the balance between pro-proliferative effector vascular endothelial growth factor (VEGF) and anti-proliferative effector tumor necrosis factor-like cytokine 1A (TL1A) is important in the modulation of endothelial cell survival and proliferation, and neovascularization. The present study aimed to explore whether the imbalance between VEGF and TL1A affected the apoptosis of human umbilical vein endothelial cells (HUVECs) exposed to high glucose conditions and then further investigated the potential mechanism. The results showed that the downregulation of VEGF in combination with the upregulation of TL1A in response to high glucose levels led to enhanced HUVEC apoptosis. Further experiments revealed that silencing high glucose-induced TL1A expression using TL1A small interfering (si)RNA or the overexpression of VEGF by transfection with VEGF DNA resulted in a reduced HUVEC apoptosis rate compared with the controls. The effects occurred by attenuating and activating the phosphoinositide 3-kinase/Akt/endothelial nitric oxide synthase pathway, respectively. In addition, VEGF and TL1A inhibited each other in hyperglycemia. In conclusion, these findings provide theoretical support for the further investigation of novel therapeutic strategies designed to maintain the balance between VEGF and TL1A and, thus, to prevent the onset and progression of endothelial cell apoptosis in response to high glucose stimuli.

Liu L.-H.,Sun Yat Sen University | Liu L.-H.,Key Laboratory of Tropical Disease Control | He H.-J.,Xiangnan University | Lv Z.-Y.,Sun Yat Sen University | And 15 more authors.
Parasitology Research | Year: 2013

Galectin plays an important role in host-parasite interactions. In this study, we identified a novel gene encoding galectin-10 (AcGal-10) from the cDNA library of Angiostrongylus cantonensis and characterized its biological role in the parasite. Sequence and phylogeny analysis showed that AcGal-10 is related to other galectin family members with the conserved loci (H84-D 86-R88-V96-N98-W105- E108-R110). The mRNA level of AcGal-10 was expressed in reactive oxygen stress radicals. We have identified two proteins of A. cantonensis galectin-10 gene, one of which was reported (AcGAL10-W) and the others is AcGAL-10-M. In addition, recombinant AcGal-10 (rAcGal-10) was constructed into the pGEX-4T-1 plasmid, purified, and finally confirmed by SDS-PAGE and LC-MS. Hemagglutination assay showed that the minimum concentration of rAcGAL10-W and rAcGAL10-M required for the hemagglutination of BALB/c mice erythrocyte was 25 μg/mL, and the carbohydrate-binding ability showed no difference between rAcGAL10-W and rAcGAL10-M. The mRNA levels of AcGal-10 were indeed expressed higher after stimulation with H2O2 and recombinant A. cantonensis galectin-10. A mutation of AcGal-10 was also found, but there was no significant difference compared with the wild type. Furthermore, we also confirmed that recombinant AcGal-10 plays a role in the activation of the microglia. In conclusion, the report here showed that AcGal-10 may be an important molecule related to infection of A. cantonensis. © 2012 Springer-Verlag Berlin Heidelberg.

Song L.-G.,Sun Yat Sen University | Song L.-G.,Key Laboratory of Tropical Disease Control | Wu X.-Y.,Fudan University | Sacko M.,National Health Research Institute | And 2 more authors.
Parasitology Research | Year: 2016

Schistosomiasis is a snail-borne disease caused by worms of the genus Schistosoma. Worldwide, human schistosomiasis remains a serious public health problem, threatening ∼800 million people in 78 countries with a loss of 70 million disability-adjusted life years. Schistosoma japonicum is the only human blood fluke that occurs in China. As one of the countries suffering greatly from schistosomiasis, over the past 65 years, China has made great strides in controlling schistosomiasis, blocking the transmission of S. japonicum in five provinces, remarkably reducing transmission intensities in the other seven endemic provinces, and China is currently preparing to move toward the elimination of this disease before 2025. However, while on the road to schistosomiasis elimination, emerging challenges merit attention, including severe advanced cases, increased movements of population and livestock, large-area distribution of intermediate host snails, limitations of new drug developments and no vaccine available, as well as imported schistosomiasis and its potential risk. © 2016 Springer-Verlag Berlin Heidelberg

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