Publications by authors named "Hong-Juan Peng"

70 Publications

SAG1 targeting host cell S100A6 for parasite invasion and host immunity.

iScience 2021 Dec 26;24(12):103514. Epub 2021 Nov 26.

Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province 510515, P R China.

surface antigen 1 (SAG1) is a surface protein of tachyzoites, which plays a crucial role in infection and host cell immune regulation. However, how SAG1 regulates these processes remains elucidated. We utilized the biotin ligase -TurboID fusion with SAG1 to identify the host proteins interacting with SAG1, and identified that S100A6 was co-localized with SAG1 when attached to the host cell. S100A6, either knocking down or blocking its functional epitopes resulted in inhibited parasites invasion. Meanwhile, S100A6 overexpression in host cells promoted infection. We further verified that SAG1 could inhibit the interaction of host cell vimentin with S100A6 for cytoskeleton organization during invasion. As an immunogen, SAG1 could promote the secretion of tumor necrosis factor alpha (TNF-α) through S100A6-Vimentin/PKCθ-NF-κB signaling pathway. In summary, our findings revealed a mechanism for how SAG1 functioned in parasitic invasion and host immune regulation.
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http://dx.doi.org/10.1016/j.isci.2021.103514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8671940PMC
December 2021

A uracil auxotroph Toxoplasma gondii exerting immunomodulation to inhibit breast cancer growth and metastasis.

Parasit Vectors 2021 Dec 11;14(1):601. Epub 2021 Dec 11.

Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, 510515, People's Republic of China.

Background: Breast cancer is the most common cause of cancer-related death among women, and prognosis is especially poor for patients with triple-negative breast cancer (TNBC); therefore, there is an urgent need for new effective therapies. Recent studies have demonstrated that the uracil auxotroph Toxoplasma gondii vaccine displays anti-tumor effects. Here, we examined the immunotherapy effects of an attenuated uracil auxotroph strain of T. gondii against 4T1 murine breast cancer.

Methods: We constructed a uracil auxotroph T. gondii RH strain via orotidine 5'-monophosphate decarboxylase gene deletion (RH-Δompdc) with CRISPR/Cas9 technology. The strain's virulence in the T. gondii-infected mice was determined in vitro and in vivo by parasite replication assay, plaque assay, parasite burden detection in mice peritoneal fluids and survival analysis. The immunomodulation ability of the strain was evaluated by cytokine detection. Its anti-tumor effect was evaluated after its in situ inoculation into 4T1 tumors in a mouse model; the tumor volume was measured, and the 4T1 lung metastasis was detected by hematoxylin and eosin and Ki67 antibody staining, and the cytokine levels were measured by an enzyme-linked immunosorbent assay.

Results: The RH-Δompdc strain proliferated normally when supplemented with uracil, but it was unable to propagate without the addition of uracil and in vivo, which suggested that it was avirulent to the hosts. This mutant showed vaccine characteristics that could induce intense immune responses both in vitro and in vivo by significantly boosting the expression of inflammatory cytokines. Inoculation of RH-Δompdc in situ into the 4T1 tumor inhibited tumor growth, reduced lung metastasis, promoted the survival of the tumor-bearing mice and increased the secretion of Th1 cytokines, including interleukin-12 (IL-12) and interferon-γ (INF-δ), in both the serum and tumor microenvironment (TME).

Conclusion: Inoculation of the uracil auxotroph RH-Δompdc directly into the 4T1 tumor stimulated anti-infection and anti-tumor immunity in mice, and resulted in inhibition of tumor growth and metastasis, promotion of the survival of the tumor-bearing mice and increased secretion of IL-12 and IFN-γ in both the serum and TME. Our findings suggest that the immunomodulation caused by RH-Δompdc could be a potential anti-tumor strategy.
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http://dx.doi.org/10.1186/s13071-021-05032-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8665513PMC
December 2021

iTRAQ-Based Phosphoproteomic Analysis of Tachyzoites Provides Insight Into the Role of Phosphorylation for its Invasion and Egress.

Front Cell Infect Microbiol 2020 26;10:586466. Epub 2020 Nov 26.

Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical University, Xuzhou, China.

The invasion and egress are two key steps in lytic cycle vital to the propagation of infection, and phosphorylation is believed to play important roles in these processes. However, the phosphoproteome of at these two stages has not been characterized. In this study, we profiled the phosphoproteome of tachyzoites at the stages of "just invading" (JI) and "prior to egress" (PE) based on iTRAQ quantitative analysis, in which a total of 46 phosphopeptides, 42 phosphorylation sites, and 38 phosphoproteins were detected. In the comparison of PE vs. JI, 10 phosphoproteins were detected with their phosphorylation level significantly changed, and four of them were demonstrated to be significantly down-regulated at the transcriptional level. Bioinformatic analysis of these identified phosphoproteins suggested that phosphorylation-mediated modulation of protein function was employed to regulate the pathway of toxoplasmosis and metabolism and cellular processes correlated with tachyzoite's binding, location, and metabolism, and thus play vital roles in the parasite lytic cycle. Moreover, cytoskeletal network (CN)-associated Inner Membrane Complex (IMC1, IMC4, IMC6 and IMC12), Intravascular Network (IVN)-related GRAs (GRA2, GRA3, GRA7 and GRA12), and Parasitophorous Vacuole Membrane (PVM)-localized ROP5 were shown to be enriched at the central nodes in the protein interaction network generated by bioinformatic analysis, in which the phosphorylation level of IMC4, GRA2, GRA3, and GRA12 were found to be significantly regulated. This study revealed the main cellular processes and key phosphoproteins crucial for the invasion and egress of , which will provide new insights into the developmental biology of and contribute to the understanding of pathogen-host interaction from the parasite perspective.
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http://dx.doi.org/10.3389/fcimb.2020.586466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756149PMC
June 2021

Strain-specific disruption of interferon-stimulated N-myc and STAT interactor (NMI) function by type I ROP18 in human cells.

Parasitology 2020 11 30;147(13):1433-1442. Epub 2020 Jul 30.

Department of Biological Sciences, Dietrich School of Arts and Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania15260, USA.

Toxoplasma gondii rhoptry protein TgROP18 is a polymorphic virulence effector that targets immunity-related GTPases (IRGs) in rodents. Given that IRGs are uniquely diversified in rodents and not in other T. gondii intermediate hosts, the role of TgROP18 in manipulating non-rodent cells is unclear. Here we show that in human cells TgROP18I interacts with the interferon-gamma-inducible protein N-myc and STAT interactor (NMI) and that this is a property that is unique to the type I TgROP18 allele. Specifically, when expressed ectopically in mammalian cells only TgROP18I co-immunoprecipitates with NMI in IFN-γ-treated cells, while TgROP18II does not. In parasites expressing TgROP18I or TgROP18II, NMI only co-immunoprecipitates with TgROP18I and this is associated with allele-specific immunolocalization of NMI on the parasitophorous vacuolar membrane (PVM). We also found that TgROP18I reduces NMI association with IFN-γ-activated sequences (GAS) in the IRF1 gene promoter. Finally, we determined that polymorphisms in the C-terminal kinase domain of TgROP18I are required for allele-specific effects on NMI. Together, these data further define new host pathway targeted by TgROP18I and provide the first function driven by allelic differences in the highly polymorphic ROP18 locus.
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http://dx.doi.org/10.1017/S0031182020001249DOI Listing
November 2020

Current epidemic situation of human toxocariasis in China.

Adv Parasitol 2020 5;109:433-448. Epub 2020 Feb 5.

Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China. Electronic address:

Toxocariasis is a worldwide-distributed helminthic zoonosis, which mainly results from ascarid nematodes Toxocara canis and Toxocara cati. Humans become infected by accidental ingestion of infective eggs, raw or undercooked meat containing larvae. Keeping and contacting cats and dogs, and bad hygiene situations or habits are the main risk factors for Toxocara infection in China. The seroprevalence of Toxocara spp. is reported from 12.14% to 44.83%, and the overall seroprevalence in children was 12.14% in 1993 and elevated to 19.3% in 2015. Among the 103 cases reported in China during 1983-2019, ocular larva migrans (OLM), visceral larva migrans (VLM), and neural larva migrans (NLM) occupied 92.23%, 6.80%, and 0.97% of cases, respectively. The diagnosis of toxocariasis is mainly based on the history of exposure to infective eggs or larvae, clinical manifestations, laboratory examinations, and imaging studies. As most individuals who are infected with larval Toxocara, are unaware of their infections, patients with mild signs as described under covert toxocariasis (CT) can recover spontaneously, and treatment may not be necessary. Albendazole is the preferred treatment for patients with VLM; steroids, such as prednisolone combined with albendazole, are frequently used in treating patients with OLM, and surgery serves as an alternative treatment; thiabendazole is effective in treating patients with NLM. The true number of cases and prevalence of toxocariasis in China seems to be underestimated and neglected because of the lack of population-based epidemiological studies and insufficient clinical awareness of this disease, which are aspects that need to be improved by the Chinese government.
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http://dx.doi.org/10.1016/bs.apar.2020.01.016DOI Listing
May 2021

Characteristics of and Public Health Responses to the Coronavirus Disease 2019 Outbreak in China.

J Clin Med 2020 Feb 20;9(2). Epub 2020 Feb 20.

Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China.

In December 2019, cases of unidentified pneumonia with a history of exposure in the Huanan Seafood Market were reported in Wuhan, Hubei Province. A novel coronavirus, SARS-CoV-2, was identified to be accountable for this disease. Human-to-human transmission is confirmed, and this disease (named COVID-19 by World Health Organization (WHO)) spread rapidly around the country and the world. As of 18 February 2020, the number of confirmed cases had reached 75,199 with 2009 fatalities. The COVID-19 resulted in a much lower case-fatality rate (about 2.67%) among the confirmed cases, compared with Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). Among the symptom composition of the 45 fatality cases collected from the released official reports, the top four are fever, cough, short of breath, and chest tightness/pain. The major comorbidities of the fatality cases include hypertension, diabetes, coronary heart disease, cerebral infarction, and chronic bronchitis. The source of the virus and the pathogenesis of this disease are still unconfirmed. No specific therapeutic drug has been found. The Chinese Government has initiated a level-1 public health response to prevent the spread of the disease. Meanwhile, it is also crucial to speed up the development of vaccines and drugs for treatment, which will enable us to defeat COVID-19 as soon as possible.
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http://dx.doi.org/10.3390/jcm9020575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074453PMC
February 2020

Genome-Wide CRISPR Screen Identifies Host Factors Required by Infection.

Front Cell Infect Microbiol 2019 22;9:460. Epub 2020 Jan 22.

Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Pathogen Biology, School of Public Health, Southern Medical University, Guangzhou, China.

are obligate intracellular protoza, and due to their small genome and limited encoded proteins, they have to exploit host factors for entry, replication, and dissemination. Such host factors can be defined as host dependency factors (HDFs). Though HDFs are inessential for cell viability, they are critical for pathogen infection, and potential ideal targets for therapeutic intervention. However, information about these HDFs required by infection is highly deficient. In this study, the genes of human foreskin fibroblast (HFF) cells were comprehensively edited using the lentiviral CRISPR-Cas9-sgRNA library, and then the lentivirus-treated cells were infected with at multiplication of infection 1 (MOI = 1) for 10 days to identify HDFs essential for infection. The survival cells were harvested and sent for sgRNA sequencing. The sgRNA sequence matched genes or miRNAs were potential HDFs. Some cells in the lentivirus-treated group could survive longer than those in the untreated control group after infection. From a pool of 19,050 human genes and 1,864 human pri-miRNAs, 1,193 potential HDFs were identified, including 1,183 genes and 10 pri-miRNAs (corresponding with 17 mature miRNAs). Among them, seven genes and five mature miRNAs were validated with siRNAs, miRNA inhibitors, and mimics, respectively. Bioinformatics analysis revealed that, among the 1,183 genes, 53 potential HDFs were associated with regulation of host actin cytoskeleton and 23 potential HDFs coded immune negative regulators. This result indicated that actin dynamics were indispensable for infection, and some host immune negative regulators may be involved in disarming host defenses. Our findings contribute to the current limited knowledge about host factors required by infection and provide us with new targets for medication therapy and vaccine exploitation.
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http://dx.doi.org/10.3389/fcimb.2019.00460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6987080PMC
August 2020

A Review on Dengue Vaccine Development.

Vaccines (Basel) 2020 Feb 2;8(1). Epub 2020 Feb 2.

Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China.

Dengue virus (DENV) has become a global health threat with about half of the world's population at risk of infection. Although the disease caused by DENV is self-limiting in the first infection, the antibody-dependent enhancement (ADE) effect increases the mortality in the second infection with a heterotypic virus. Since there is no specific efficient medicine in treatment, it is urgent to develop vaccines to prevent infection and disease progression. Currently, only a live attenuated vaccine, chimeric yellow fever 17D-tetravalent dengue vaccine (CYD-TDV), has been licensed for clinical use in some countries, and many candidate vaccines are still under research and development. This review discusses the progress, strengths, and weaknesses of the five types of vaccines including live attenuated vaccine, inactivated virus vaccine, recombinant subunit vaccine, viral vectored vaccine, and DNA vaccine.
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http://dx.doi.org/10.3390/vaccines8010063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159032PMC
February 2020

Analysis of the Differential Exosomal miRNAs of DC2.4 Dendritic Cells Induced by Infection.

Int J Mol Sci 2019 Nov 5;20(21). Epub 2019 Nov 5.

Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China.

is an intracellular parasite that infects humans and other warm-blooded animals. Exosomes are endocytic-derived vesicles released by cells, representing an important mode of intercellular communication. In exosomes, specific molecules of proteins, lipids, and mRNAs or miRNAs have been detected, some of which are capable of transferring biologically active molecules to recipient cells. Dendritic cells (DCs) are the only antigen-presenting cells (APCs) that activate the initial immune response. In this study, high-throughput sequencing was used to analyze the exosomal miRNA profile of DC2.4 cells infected with for 28 h, compared with those of uninfected DC2.4 cells. Differential exosomal miRNAs (DEmiRs) from these two cell groups were analyzed. Through high-throughput sequencing, 3434 DEmiRs were obtained, and 12 stably enriched DEmiRNAs were verified by Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR) and selected for further analysis. The target genes of these 12 miRNAs were predicted with online analysis software and subjected to bioinformatics analyses including protein-protein interaction (PPI) network analysis, key driver analysis (KDA), gene ontology (GO) enrichment, and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis. These DEmiRs were found to be associated with a variety of biological processes and signaling pathways involved in host ubiquitin system, innate immunity, biosynthesis, and transferase activity and could be potential biomarkers for infection.
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http://dx.doi.org/10.3390/ijms20215506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862309PMC
November 2019

Application of the Scorpion Neurotoxin AaIT against Insect Pests.

Int J Mol Sci 2019 Jul 15;20(14). Epub 2019 Jul 15.

Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, Southern Medical University, Guangzhou, Guangdong Province 510515, China.

Hector insect toxin (AaIT), an insect-selective toxin, was identified in the venom of the scorpion . The exclusive and specific target of the toxin is the voltage-gated sodium channels of the insect, resulting in fast excitatory paralysis and even death. Because of its strict toxic selectivity and high bioactivity, AaIT has been widely used in experiments exploring pest bio-control. Recombinant expression of AaIT in a baculovirus or a fungus can increase their virulence to insect pests and diseases vectors. Likewise, transgenic plants expressing AaIT have notable anti-insect activity. AaIT is an efficient toxin and has great potential to be used in the development of commercial insecticides.
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http://dx.doi.org/10.3390/ijms20143467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678123PMC
July 2019

Expression of Bacillus thuringiensis toxin Cyt2Ba in the entomopathogenic fungus Beauveria bassiana increases its virulence towards Aedes mosquitoes.

PLoS Negl Trop Dis 2019 07 15;13(7):e0007590. Epub 2019 Jul 15.

Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, Southern Medical University, Guangzhou, Guangdong Province, China.

Background: The entomopathogenic fungus Beauveria bassiana has been widely used to kill mosquito larvae and adults in the laboratory and field. However, its slow action of killing has hampered its widespread application. In our study, the B. bassiana fungus was genetically modified to express the Bacillus thuringiensis (Bt) toxin Cyt2Ba to improve its efficacy in killing mosquitoes.

Methodology/principal Findings: The efficacy of the wild type (WT) of B. bassiana and a transgenic strain expressing Cyt2Ba toxin (Bb-Cyt2Ba) was evaluated against larval and adult Aedes mosquitoes (Aedes aegypti and Aedes albopictus) using insect bioassays. The Bb-Cyt2Ba displayed increased virulence against larval and adult Aedes mosquitoes compared with the WT: for Ae. aegypti adults, the median lethal time (LT50) was decreased by 33% at the concentration of 1× 108 conidia/ml, 19% at 1× 107 conidia/ml and 47% at 1× 106 conidia/ml. The LT50 for Ae. albopictus adults was reduced by 20%, 23% and 29% at the same concentrations, respectively. The LT50 for Ae. aegypti larvae was decreased by 42% at 1× 107 conidia/ml and 25% at 1× 106 conidia/ml, and that for Ae. albopictus larvae was reduced by 33% and 31% at the same concentrations, respectively. In addition, infection with Bb-Cyt2Ba resulted in a dramatic reduction in the fecundity of Aedes mosquitoes.

Conclusions/significance: In conclusion, our study demonstrated that the virulence of B. bassiana against mosquitoes can be significantly improved by introducing the Bt toxin gene Cyt2Ba into the genome to express the exogenous toxin in the fungus. The transgenic strain Bb-Cyt2Ba significantly reduced the survival and fecundity of Ae. aegypti and Ae. albopictus compared with the WT strain, which suggested that this recombinant B. bassiana has great potential for use in mosquito control.
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http://dx.doi.org/10.1371/journal.pntd.0007590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667155PMC
July 2019

Toxoplasma gondii ROP18 inhibits human glioblastoma cell apoptosis through a mitochondrial pathway by targeting host cell P2X1.

Parasit Vectors 2019 Jun 4;12(1):284. Epub 2019 Jun 4.

Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China.

Background: Apoptosis plays a critical role in the embryonic development, homeostasis of immune system and host defense against intracellular microbial pathogens. Infection by the obligate intracellular pathogen Toxoplasma gondii can both inhibit and induce host cell apoptosis; however, the parasitic factors involved remain unclear. The T. gondii virulence factor ROP18 (TgROP18) has been reported to regulate host cell apoptosis; nevertheless, results for this regulation have been rarely reported or have provided contradictory findings. Human purinergic receptor 1 (P2X1) is an ATP-gated ion channel that responds to ATP stimulation and functions in cell apoptosis mediation. The precise roles of TgROP18 in T. gondii pathogenesis, and the relationship between TgROP18 and host P2X1 in host cell apoptosis are yet to be revealed.

Methods: Apoptosis rates were determined by flow cytometry (FCM) and TUNEL assay. The interaction between TgROP18 and the host P2X1 was measured by fluorescence resonance energy transfer (FRET) and co-immunoprecipitation (co-IP) assay. Calcium influx and mitochondrial membrane depolarization were determined by FCM after JC-1 staining. The translocation of cytochrome C (Cyt C), Bax and Bcl2 proteins, expression of the apoptotic proteins PARP and caspase activation were detected by western blotting.

Results: The apoptosis rates of glial or immune cells (human SF268, mouse RAW264.7 and human THP-1 cells) infected by any T. gondii strain (RH-type I, ME49-type II and VEG-type III) were significantly inhibited compared with their uninfected controls. TgROP18 inhibited ATP-induced apoptosis of SF268 with P2X1 expression, but had no effect on RAW264.7 or THP-1 cells without detectable P2X1 expression. It was further identified that TgROP18 interacted with P2X1, and overexpression of ROP18 in COS7 cells significantly inhibited cell apoptosis mediated by P2X1. Moreover, TgROP18 also inhibited P2X1-mediated Ca influx, translocation of cytochrome C from the mitochondria to the cytosol, and ATP-triggered caspase activation.

Conclusions: Toxoplasma gondii infection inhibits ATP-induced host cell apoptosis, regardless of strain virulence and host cell lines. TgROP18 targets the purinergic receptor P2X1 of the SF268 human neural cells and inhibits ATP-induced apoptosis through the mitochondrial pathway, suggesting a sensor role for the host proapoptotic protein P2X1 in this process.
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http://dx.doi.org/10.1186/s13071-019-3529-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547611PMC
June 2019

iTRAQ-based phosphoproteomic analysis reveals host cell's specific responses to Toxoplasma gondii at the phases of invasion and prior to egress.

Biochim Biophys Acta Proteins Proteom 2019 03 18;1867(3):202-212. Epub 2018 Dec 18.

Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China. Electronic address:

Protein phosphorylation plays a key role in host cell-T. gondii interaction. However, the phosphoproteome data of host cell at various phases of T. gondii infection has not been thoroughly described. In this study, we assessed the host phosphoproteome data with isobaric tags for relative and absolute quantification (iTRAQ) method during the phases of T. gondii invasion (30 min post infection, PI) and prior to egress (28 h PI). Our iTRAQ analysis revealed a total of 665 phosphoproteins, among which the significantly regulated phosphoproteins in different between-group comparisons were further analyzed. Functional analysis of these significantly regulated phosphoproteins suggested that T. gondii modulated host cell processes through phosphorylation including cell cycle regulation, inducing apoptosis, blocking the synthesis of some inflammatory factors, mediating metabolism to support its proliferation at the infection phase prior to egress, and utilizing membrane and energy from host cell, reorganizing cytoskeleton to favor its invasion and PV formation at the phase of invasion. The phosphorylation level of Smad2, CTNNA1, and HSPB1 identified with western blot revealed a consistent trend of change with iTRAQ result. These newly identified and significantly regulated phosphoproteins from our phosphoproteome data may provide new clues to unravel the host cell's complex reaction against T. gondii infection and the interaction between the host cell and T. gondii.
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http://dx.doi.org/10.1016/j.bbapap.2018.12.004DOI Listing
March 2019

Genome-Wide Bimolecular Fluorescence Complementation-Based Proteomic Analysis of ROP18's Human Interactome Shows Its Key Role in Regulation of Cell Immunity and Apoptosis.

Front Immunol 2018 5;9:61. Epub 2018 Feb 5.

Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China.

rhoptry protein ROP18 (ROP18) is a key virulence factor secreted into the host cell during invasion, where it modulates the host cell response by interacting with its host targets. However, only a few ROP18 targets have been identified. In this study, we applied a high-throughput protein-protein interaction (PPI) screening in human cells using bimolecular fluorescence complementation (BiFC) to identify the targets of Type I strain ROP18 (ROP18) and Type II strain ROP18 (ROP18). From a pool of more than 18,000 human proteins, 492 and 141 proteins were identified as the targets of ROP18 and ROP18, respectively. Gene ontology, search tool for the retrieval of interacting genes/proteins PPI network, and Ingenuity pathway analyses revealed that the majority of these proteins were associated with immune response and apoptosis. This indicates a key role of ROP18 in manipulating host's immunity and cell apoptosis, which might contribute to the immune escape and successful parasitism of the parasite. Among the proteins identified, the immunity-related proteins N-myc and STAT interactor, IL20RB, IL21, ubiquitin C, and vimentin and the apoptosis-related protein P2RX1 were further verified as ROP18 targets by sensitized emission-fluorescence resonance energy transfer (SE-FRET) and co-immunoprecipitation. Our study substantially contributes to the current limited knowledge on human targets of ROP18 and provides a novel tool to investigate the function of parasite effectors in human cells.
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http://dx.doi.org/10.3389/fimmu.2018.00061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5807661PMC
February 2019

Diagnostic Function of 3D Optical Coherence Tomography Images in Diagnosis of Vogt-Koyanagi-Harada Disease at Acute Uveitis Stage.

Med Sci Monit 2018 Feb 3;24:687-697. Epub 2018 Feb 3.

Department of Ophthalmology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China (mainland).

BACKGROUND This study analyzed the macular 3D-OCT images of Vogt-Koyanagi-Harada disease (VKH) in uveitis, explored the characteristics of 3D-OCT images of the macular region of VKH, and assessed which characteristics contribute most to VKH diagnosis. MATERIAL AND METHODS The 3D-OCT examination of 25 cases of VKH was performed on the macular area, and the image characteristics were analyzed. RESULTS Our study included a total of 50 eyes from 25 cases of VKH patients, 10 males and 15 females, aged 17 to 64 years, mean (39.44±11.60) years old. According to OCT B-scan images, 49 (98%) eyes had ERD, 49 (98%) eyes had nerve retinal edema, 36 (72%) eyes had endometrium-like structure (including cysts), 5 (10%) eyes had RPE folds, 35 (70%) eyes had changes in the internal septum, 49 (98%) eyes had RPE monolayer structure outside the ERD region. In ILM-RPE thickness, 49 (98%) eyes had retinal irregular thickening and 31 (62%) eyes had radial stripe changes. In ILM contour figure, 50 eyes (100%) showed exceptional uplift, 5 (10%) eyes had small focal uplift for PED on the RPE surface, and 48 (96%) eyes had wavy ups and downs. CONCLUSIONS In OCT B-scan imaging, the ERT, retinal edema of the retina, and the RPE monolayer structure outside the range are most likely to occur in VKH. The ILM-RPE thickness chart in 3D reconstruction showed irregular thickening of the retina. The ILM contour graph showed abnormal uplift, and RPE surface wavy ups and downs in VKH most likely to occur.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5807914PMC
http://dx.doi.org/10.12659/msm.905931DOI Listing
February 2018

Roles of Interferons in Pregnant Women with Dengue Infection: Protective or Dangerous Factors.

Can J Infect Dis Med Microbiol 2017 7;2017:1671607. Epub 2017 Sep 7.

Guangdong Provincial Key Laboratory of Tropical Disease Research and Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, School of Public Health and Tropical Medicine, Southern Medical University, No. 1023 South Shatai Road, Guangzhou, Guangdong Province 510515, China.

Dengue infection is a serious public health problem in tropical and subtropical areas. With the recent outbreaks of Zika disease and its reported correlation with microcephaly, the large number of pregnancies with dengue infection has become a serious concern. This review describes the epidemiological characteristics of pregnancy with dengue and the initial immune response to dengue infection, especially in IFNs production in this group of patients. Dengue is much more prevalent in pregnant women compared with other populations. The severity of dengue is correlated with the level of IFNs, while the serum IFN level must be sufficiently high to maintain the pregnancy and to inhibit virus replication.
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http://dx.doi.org/10.1155/2017/1671607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610849PMC
September 2017

The Differential Expression and Possible Function of Long Noncoding RNAs in Liver Cells Infected by Dengue Virus.

Am J Trop Med Hyg 2017 Dec 28;97(6):1904-1912. Epub 2017 Sep 28.

Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, and Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, China.

The function of long noncoding RNAs (lncRNAs) in liver injury resulted by dengue virus (DENV) infection have not yet been explored. The differential expression profiles of lncRNAs (as well as mRNAs) in the L-02 liver cells infected by DENV1, DENV2, or uninfected were compared and analyzed after a high throughput RNA seq. The significantly up-regulated and down-regulated lncRNAs (or mRNAs) resulted by DENV infection were identified with a cutoff value at log2 (ratio) ≥ 1.5 and log2 (ratio) ≤ -1.5 (ratio = the reads of the lncRNAs or mRNAs from the infection groups divided by the reads from the control group). Several differentially expressed lncRNAs were verified with reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). Target gene analysis, pre-miRNA prediction, and the lncRNA-mRNA co-expression network construction were performed to predict the function of the differentially expressed lncRNAs. The differentially expressed lncRNAs were associated with biosynthesis, DNA/RNA related processes, inhibition of estrogen signaling pathway, sterol biosynthetic process, protein dimerization activity, vesicular fraction in DENV1 infection group; and with protein secretion, methyltransferase process, host cell cytoskeleton reorganization and the small GTPase Ras superfamily, inhibition of cell proliferation, induction of apoptosis in DENV2 infection. LncRNAs might be novel diagnostic markers and targets for further researches on dengue infection and liver injury resulted by dengue virus.
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http://dx.doi.org/10.4269/ajtmh.17-0307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805055PMC
December 2017

Spatiotemporal Analysis of the Malaria Epidemic in Mainland China, 2004-2014.

Am J Trop Med Hyg 2017 Aug;97(2):504-513

Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, and Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, China.

The purpose of this study is to characterize spatiotemporal heterogeneities in malaria distribution at a provincial level and investigate the association between malaria incidence and climate factors from 2004 to 2014 in China to inform current malaria control efforts. National malaria incidence peaked (4.6/100,000) in 2006 and decreased to a very low level (0.21/100,000) in 2014, and the proportion of imported cases increased from 16.2% in 2004 to 98.2% in 2014. Statistical analyses of global and local spatial autocorrelations and purely spatial scan statistics revealed that malaria was localized in Hainan, Anhui, and Yunnan during 2004-2009 and then gradually shifted and clustered in Yunnan after 2010. Purely temporal clusters shortened to less than 5 months during 2012-2014. The two most likely clusters detected using spatiotemporal analysis occurred in Anhui between July 2005 and November 2007 and Yunnan between January 2010 and June 2012. Correlation coefficients for the association between malaria incidence and climate factors sharply decreased after 2010, and there were zero-month lag effects for climate factors during 2010-2014. Overall, the spatiotemporal distribution of malaria in China changed from relatively scattered (2004-2009) to relatively clustered (2010-2014). As the proportion of imported cases increased, the effect of climate factors on malaria incidence has gradually become weaker since 2011. Therefore, new warning systems should be applied to monitor resurgence and outbreaks of malaria in mainland China, and quarantine at borders should be reinforced to control the increasingly trend of imported malaria cases.
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http://dx.doi.org/10.4269/ajtmh.16-0711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5544075PMC
August 2017

Phosphoproteome of Infected Host Cells Reveals Specific Cellular Processes Predominating in Different Phases of Infection.

Am J Trop Med Hyg 2017 Jul;97(1):236-244

Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, and Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, 510515, China.

The invasion of tachyzoites into the host cell results in extensive host cell signaling activation/deactivation that is usually regulated by the phosphorylation/dephosphorylation. To elucidate how regulates host cell signal transduction, the comparative phosphoproteome of stable isotope labeling with amino acids in cell culture-labeled human foreskin fibroblast cells was analyzed. The cells were grouped (Light [L], Medium [M], and Heavy [H] groups) based on the labeling isotope weight and were infected with for different lengths of time (L: 0 hour; M: 2 hours; and H: 6 hours). A total of 892 phosphoproteins were identified with 1,872 phosphopeptides and 1,619 phosphorylation sites. The M versus L comparison revealed 694 significantly regulated phosphopeptides (436 upregulated and 258 downregulated). The H versus L comparison revealed 592 significantly regulated phosphopeptides (146 upregulated and 446 downregulated). The H versus M comparison revealed 794 significantly regulated phosphopeptides (149 upregulated and 645 downregulated). At 2 and 6 hours post- infection, the most predominant host cell reactions were cell cycle regulation and cytoskeletal reorganization, which might be required for the efficient invasion and multiplication of . Similar biological process profiles but different molecular function categories of host cells infected with for 2 and 6 hours, which suggested that the host cell processes were not affected significantly by infection but emphasized some differences in specific cellular processes at this two time points. Western blotting verification of some significantly regulated phosphoprotein phosphorylation sites was consistent with the mass spectra data. This study provided new insights into and further understanding of pathogen-host interactions from the host cell perspective.
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http://dx.doi.org/10.4269/ajtmh.16-0901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5508905PMC
July 2017

[Larvicidal activity of recombinant Escherichia coli expressing scorpion neurotoxin AaIT or B.t.i toxin Cyt2Ba against mosquito larvae and formulations for enhancing the effects].

Nan Fang Yi Ke Da Xue Xue Bao 2017 Jun;37(6):750-754

Department of Pathogen Biology/Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China. E-mail:

Objective: To assess the larvicidal effects of recombinant Escherichia coli expressing scorpion neurotoxin AaIT or Bacillus thuringiensis subsp israelensis (B.t.i) toxin Cyt2Ba against the second instar larvae of Culex pipiensquinquefasciatus and Aedes albopictus and compare different formulations for their larvicidal effects.

Methods: The AaIT- or Cyt2Ba-coding sequences were cloned into pET28a(+) and the recombinant plasmids were transformed into E. coli BL21(DE3). After induction with IPTG, the recombinant proteins expressed by the recombinant E. coli were detected and identified by SDS-PAGE and Western blotting, respectively. The larvicidal activity of the bacterial suspension was tested at different concentrations against mosquitoes. The effective engineered bacteria were prepared into dry powder with different formulations, and their larvicidal activity was tested.

Results: AaIT and Cyt2Ba proteins were successfully expressed in E. coli. The recombinant AaIT protein showed no virulence to the mosquito larvae. The suspension of the recombinant E. coli expressing Cyt2Ba protein exhibited a stronger killing effect on Aedes albopictus larvae than on Culex pipiens quinquefasciatus larvae at 48 h (P<0.001) with LC of 3.00×10 cells/mL and 1.25×10 cells/mL, respectively. The dry powder of the engineered bacteria formulated with yeast extract, wheat flour or white pepper powder at the mass ratio of 1:1 showed the strongest killing effect on mosquito larvae (P=0.044), and the formulation with white pepper powder produced a stronger killing effect than formulations with yeast extract or wheat flour (P=0.002).

Conclusion: The B.t.i Cyt2Ba protein expressed in E. coli BL21(DE3) shows a good larvicidal activity against mosquitoes, and appropriate formulations of the engineered bacteria can enhance its efficiency in mosquito control.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744137PMC
June 2017

Association between Toxoplasma gondii types and outcomes of human infection: A meta-analysis.

Acta Microbiol Immunol Hung 2017 Sep 20;64(3):229-244. Epub 2017 Jun 20.

1 Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, and Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, School of Public Health, Southern Medical University , Guangzhou, China.

The virulence and pathogenicity of various types of Toxoplasma gondii differ considerably in mice. Recent studies have claimed that similar phenomenon was observed in humans, but no relevant studies have been performed to validate this finding. In addition, reports showing association between a given T. gondii type and outcomes of human infection yielded conflicting results. To provide a more precise estimation of the association and a more reliable conclusion on this subject, we performed this meta-analysis. Relevant literatures were identified in multiple databases and selected based on strict screening. T. gondii-type proportions among different severities of infection were calculated and compared using Fisher's exact test. Pooled odds ratios (OR) were calculated. Our results showed that the difference among T. gondii-type proportions was significant (p < 0.0001). In addition, significant associations were detected between Type I strains infection and congenital toxoplasmosis (OR: 1.91, p = 0.0009), Type III strains infection and pulmonary toxoplasmosis (OR: 5.15, p = 0.04). In our subgroup analysis, Type I strains were significantly associated with cerebral toxoplasmosis in offspring (OR: 1.81, p = 0.02). This result indicated that different types of T. gondii exhibited different virulence and caused different outcomes in humans.
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http://dx.doi.org/10.1556/030.64.2017.016DOI Listing
September 2017

Scorpion neurotoxin AaIT-expressing Beauveria bassiana enhances the virulence against Aedes albopictus mosquitoes.

AMB Express 2017 Dec 9;7(1):121. Epub 2017 Jun 9.

Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, and Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, School of Public Health, Southern Medical University, Guangzhou, 510515, Guangdong Province, China.

To improve the insecticidal efficacy of this entomopathogen Beauveria bassiana, the fungus was genetically modified to express an insect-specific scorpion neurotoxin AaIT. The virulence of the recombinant B. bassiana strain (Bb-AaIT) against Aedes albopictus adults (which occurs via penetration through the cuticle during spore germination or by conidia ingestion), and the larvae (by conidia ingestion) was measured with bioassays. The median lethal concentration (LC) of Bb-AaIT against A. albopictus larvae was 313.3-fold lower on day 4 and 11.3-fold lower on day 10 than that of the wild type (WT). Through conidia feeding or body contact, Bb-AaIT killed 50% of adult female mosquitoes at 3.9- or 1.9-fold reduced concentrations on day 4 and at 2.1- or 2.4-fold reduced concentrations on day 10. Compared with the results for the WT, the median lethal time (LT) of Bb-AaIT was reduced by 28.6% at 1 × 10 conidia ml and 34.3% at 1 × 10 conidia ml in the larvae bioassay by conidia ingestion, while it decreased 32.3% at 1 × 10 conidia ml by conidia ingestion and 24.2% at 1 × 10 conidia ml by penetrating through the cuticle in the adult bioassay. All the differences were significant. Our findings indicated that Bb-AaIT had higher virulence and faster action than the WT in killing the larval and adult mosquitoes, and therefore, it is valuable for development as a commercial mosquito pesticide.
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http://dx.doi.org/10.1186/s13568-017-0422-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5466577PMC
December 2017

Risk of drug resistance in Plasmodium falciparum malaria therapy-a systematic review and meta-analysis.

Parasitol Res 2017 Feb 27;116(2):781-788. Epub 2016 Dec 27.

Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, and Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, 510515, China.

Plasmodium falciparum is responsible for the vast majority of the morbidity and mortality associated with malaria infection globally. Although a number of studies have reported the emergence of drug resistance in different therapies for P. falciparum infection, the degree of the drug resistance in different antimalarials is still unclear. This research investigated the risk of drug resistance in the therapies with different medications based on meta-analyses. Relevant original randomized control trials (RCTs) were searched in all available electronic databases. Pooled relative risks (RRs) with 95% confidence intervals (95% CIs) were used to evaluate the risk of drug resistance resulting from different treatments. Seventy-eight studies were included in the meta-analysis to compare drug resistance in the treatment of P. falciparum infections and yielded the following results: chloroquine (CQ) > sulfadoxine-pyrimethamine (SP) (RR = 3.67, p < 0.001 ), mefloquine (MQ) < SP (RR = 0.26, p < 0.001), artesunate + sulfadoxine-pyrimethamine (AS + SP) > artemether + lumefantrine (AL) (RR = 2.94, p < 0.001), dihydroartemisinin + piperaquine (DHA + PQ) < AL (RR = 0.7, p < 0.05), and non-artemisinin-based combination therapies (NACTs) > artemisinin-based combination therapies (ACTs) (RR = 1.93, p < 0.001); no significant difference was found in amodiaquine (AQ) vs. SP, AS + AQ vs. AS + SP, AS + AQ vs. AL, or AS + MQ vs. AL. These results presented a global view for the current status of antimalarial drug resistance and provided a guidance for choice of antimalarials for efficient treatment and prolonging the life span of the current effective antimalarial drugs.
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http://dx.doi.org/10.1007/s00436-016-5353-2DOI Listing
February 2017

[Secretion and Distribution of Rhoptry Protein 16 during Toxoplasma gondii Invasion into Host Cells].

Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi 2016 Jun;34(3):189-95

Objective: To examine the secretion and localization of Toxoplasma gondii Rhoptry protein 16 (ROP16) during invasion of different strains of T. gondii into host cells.

Methods: The Tgrop16 gene was amplified by PCR on the cDNA of T. gondii RH strain, subcloned into the plasmid pET-32a(+), and expressed in Escherichia coli BL21(DE3) under the induction of isopropyl β-D-1-thiogalactopyranoside. New Zealand rabbit was immuned with the expressed recombinant protein TgROP16 to produce polyclonal anti-TgROP16 antibody. The specificity and sensitivity of the polyclonal antibody were examined by Western blotting and indirect ELISA, respectively. The transcriptional and protein levels of Tgrop16 in T. gondii RH strain and Pru strain were determined by real-time PCR and Western blotting, respectively. The secretion and distribution of TgROP16 in human foreskin fibroblasts (HFFs) during the invasion by T. gondii RH strain and Pru strain were examined by indirect immunofluorescence assay (IFA).

Results: Western blotting showed a specific band at M(r) of ~100 000, indicating that the specific rabbit-derived anti-TgROP16 polyclonal antibody was capable of recognizing TgROP16. Indirect ELISA revealed a titer of 1:25 600 for the antibody. The relative expression level of Tgrop16 in Pru strain[(7.786±0.206)] was 7 times than that in RH strain[(1.000±0.110)](P<0.05) as detected by real-time PCR, and TgROP16 protein level was higher in RH strain than in Pru strain. IFA showed that TgROP16 was localized on the apical complex of the unrecruited tachyzoite of T. gondii before invasion and was secreted out of the recruited tachyzoite after invasion.

Conclusion: The anti-TgROP16 polyclonal antibody has high specificity and sensitivity. The TgROP16 protein level is higher in the RH strain than in the Pru strain. For both strains, TgROP16 is localized on the apical complex of the unrecruited tachyzoite before invasion and secreted out of the recruited tachyzoite during invasion.
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June 2016

Evaluation of aminotransferase abnormality in dengue patients: A meta analysis.

Acta Trop 2016 Apr 29;156:130-6. Epub 2015 Dec 29.

Department of Pathogen Biology, School of Public Health and Tropical Medicine, Southern Medical University, (#)1023 South Shatai Road, Guangzhou, Guangdong 510515, People's Republic of China. Electronic address:

Dengue virus is a type of flavivirus transmitted by Aedes mosquitoes. The symptoms of infection by this virus range from asymptomatic or mild symptomatic dengue fever (DF) to dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS). Significant abnormality in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) has been shown in a large number of dengue infection cases and to be indicator for liver injury provided that there are no other combined infections or liver injury. This study aims to assess the abnormal levels of liver aminotransferase in dengue patients. The related literature was searched in multiple databases, including PubMed, Embase, Google Scholar and Cochrane Library. The literature was selected through strict inclusion and exclusion criteria, and the quantitative synthesis of the liver aminotransferase abnormality was performed with R software. The fixed or random effects model was employed based on the results of the statistical test for homogeneity. In total, 15 studies were included. The proportion of AST abnormality with 95% confidence interval (95% CI) was 0.80 (95% CI: 0.56-0.92) in DHF patients and 0.75 (95% CI: 0.63-0.84) in DF patients; the proportion of ALT abnormality was 0.54 (95% CI: 0.34-0.73) in DHF patients and 0.52 (95% CI: 0.41-0.63) in DF patients. Serum ALT and AST levels may be indicators for evaluating liver injury in dengue infection and for diagnosis and treatment effect.
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http://dx.doi.org/10.1016/j.actatropica.2015.12.013DOI Listing
April 2016

[Research Advances on Toxoplasma gondii Virulence Mediating Factors].

Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi 2015 Aug;33(4):297-300

Toxoplasma gondii strains are grouped into three clonal lineages (Types I, II , and III) with different virulence. T. gondii rhoptry proteins ROP18, ROP16, and ROP5 are the major virulence factors, which are secreted into the host cell by T. gondii during invasion and mediate the strain virulence. This paper reviews the research progress of T. gondii virulence mediating factors.
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August 2015

Multiple Sources of Infection and Potential Endemic Characteristics of the Large Outbreak of Dengue in Guangdong in 2014.

Sci Rep 2015 Nov 23;5:16913. Epub 2015 Nov 23.

Guangdong Provincial Key Laboratory of Tropical Disease Research, and Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, School of Public Health and Tropical Medicine, Southern Medical University, #1023 South Shatai Road, Guangzhou, Guangdong Province, 510515, China.

A large outbreak of dengue, with the most documented cases, occurred in Guangdong China in 2014. Epidemiological studies and phylogenetic analysis of the isolated dengue virus (DENV) showed this outbreak was attributed to multiple sources and caused by at least two genotypes of DENV-1 (Genotypes I and III) and two genotypes of DENV-2 (Cosmopolitan and Asian I Genotypes). A retrospective review and phylogenetic analysis of DENV isolated in Guangdong showed that DENV-1 Genotype I strains were reported continuously during 2004-2014, Genotype III strains were reported during 2009-2014 ; DENV-2 Cosmopolitan and Asian I Genotype strains were reported continuously during 2012-2014. At least 45,171 cases were reported in this outbreak, with 65.9% of the patients in the 21-55-year-old group. A trend toward a decrease in the daily newly emerged cases lagged by approximately 20 days compared with the mosquito density curve. Several epidemiological characteristics of this outbreak and the stably sustained serotypes and genotypes of DENV isolated in Guangdong suggest that Guangdong has been facing a threat of transforming from a dengue epidemic area to an endemic area. The high temperature, drenching rain, rapid urbanization, and pandemic of dengue in Southeast Asia may have contributed to this large outbreak of dengue.
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http://dx.doi.org/10.1038/srep16913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4655357PMC
November 2015

A Systematic Review and Meta-Analysis of the Efficacy of Anti-Toxoplasma gondii Medicines in Humans.

PLoS One 2015 22;10(9):e0138204. Epub 2015 Sep 22.

Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, the People's Republic of China.

No effective drug and definitive "gold standard" treatment for Toxoplasma gondii (T. gondii) infection has been available so far, though some medicines have been commonly used in the treatment of T. gondii infection, such as spiramycin, azithromycin, traditional Chinese medicine (TCM), pyrimethamine- sulfadiazine (P-S), trimethoprim-sulfamethoxazole (TMP-SMX), and pyrimethamine-clindamycin (P-C). A systematic review and meta-analysis were performed to compare the efficacies of these conventional medicines in the treatment. Cohort studies for the treatment of acute T. gondii infection were searched from PubMed, Google Scholar, ect. All the cases number for different group extracted from each included literature were input to meta-analysis 3.13 software to calculate the pooled negative conversion rate (NCR), cure rate (CR) or vertical transmission rate based on their sample size and weight. The pooled NCR with 95% confidence intervals (CI) was used to evaluate the overall rate of a diagnosis positive result conversion to a negative result after treatment, which of spiramycin, azithromycin and TCM were 83.4% (95%CI, 72.1%-90.8%), 82.5% (95%CI, 75.9%-87.6%), and 85.5% (95%CI, 71.3%-93.3%) respectively, with no statistical difference between them. The pooled CR with 95% CI was used to evaluate the overall rate of complete disappearance of clinical symptoms for toxoplasmic encephalitis after therapy, which of P-S, TMP-SMX, and P-C were 49.8% (95%CI, 38. 8% -60.8%), 59.9% (95%CI, 48.9%-70.0%), and 47.6% (95%CI, 24.8%-71.4%) respectively, with no statistical difference between them. Primary T. gondii infection in pregnancy was treated mainly with spiramycin alone or combined with other drugs, and the pooled rate of vertical transmission was about 9.9% (95%CI, 5.9%-16.2%) after therapy. Toxoplasmic encephalitis in AIDS patients was usually treated with sulfonamides combined with other drugs and the pooled CR was 49.4% (95%CI, 37.9%-60.9%).
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0138204PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4578932PMC
May 2016

Association between Liver Fluke Infection and Hepatobiliary Pathological Changes: A Systematic Review and Meta-Analysis.

PLoS One 2015 17;10(7):e0132673. Epub 2015 Jul 17.

Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong, the People's Republic of China.

Objective: To provide information about the role of liver fluke infection as a risk factor for hepatobiliary pathological changes and promote awareness among the people living in endemic areas, a systematic review and meta-analysis based on published studies was conducted to examine the association between liver fluke infection and hepatobiliary pathological changes.

Methods: Relevant original literature was searched in multiple literature databases, including PubMed, Cochrane, Clinical Evidence, Trip Database, Clinical Trials, Current Controlled Trials, Web of Science, the China National Knowledge Infrastructure (CNKI) database, and the Wanfang academic journal full-text database. Studies were selected based on strict screening with inclusion and exclusion criteria. Tests of heterogeneity, sensitivity and publication bias were performed with the Review Manager software, version 5.3, and meta-regression analyses were performed with the Stata software, version 11.0 (Stata Corporation, College Station, TX, USA). Pooled risk ratios (RRs) and odds ratios (ORs) with their 95% confidence intervals (95% CIs) were calculated and used to evaluate the risk of hepatobiliary pathological changes resulting from liver fluke infection. Linear trend analyses were conducted to determine the dose-response relationship using IBM SPSS Statistics 20.0.

Result: A total of 36 studies were included in the meta-analysis. Significant associations were found between liver fluke infection and cholangitis or cholecystitis (RR: 7.80, P<0.001; OR: 15.98, P<0.001), cholelithiasis (RR: 2.42, P = 0.03; OR: 4.96, P = 0.03), hepatocellular carcinoma (OR: 4.69, P<0.001) and cholangiocarcinoma (RR: 10.43, P<0.001; OR: 4.37, P<0.001). In addition, heavier infection was significantly associated with higher incidence of hepatobiliary pathological changes (P<0.05). However, cirrhosis was not significantly associated with liver fluke infection (RR: 3.50, P = 0.06; OR: 5.79, P = 0.08). The statistical heterogeneity was significant, no significant difference was observed in the sensitivity analysis, and no publication bias was found.

Conclusion: The meta-analysis found that liver fluke infection was significantly associated with cholangitis, cholecystitis, cholelithiasis, hepatocellular carcinoma and cholangiocarcinoma and that more severe infection was associated with higher incidence. However, the association between liver fluke infection and cirrhosis was not significant.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0132673PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506038PMC
May 2016

[Observation of the Feline Intestinal Epithelial Cell Infected with Toxoplasma gondii].

Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi 2015 Feb;33(1):32-4

Small intestine samples of neonatal cat were aseptically collected from the jejunum-ileum region and digested with collagenase XI/dispase I. Immunohistochemistry results showed that feline intestinal epithelial cells were successfully isolated and could be cultured. Cytokeratin was positive in the cytoplasm of feline intestinal epithelial cells. The cells were infected with the bradyzoites of Toxoplasma gondii Prugniaud strain, and the rupture of the cells was observed on the 72nd day post-infection. The sexual stage of T. gondii did not occur, however.
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February 2015
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