Publications by authors named "Jianping Cao"

234 Publications

Comparative proteomics reveals Cryptosporidium parvum manipulation of the host cell molecular expression and immune response.

PLoS Negl Trop Dis 2021 Nov 24;15(11):e0009949. Epub 2021 Nov 24.

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research); Key Laboratory of Parasite and Vector Biology, National Health Commission of People's Republic of China; WHO Collaborating Center for Tropical Diseases, Shanghai, China.

Cryptosporidium is a life-threating protozoan parasite belonging to the phylum Apicomplexa, which mainly causes gastroenteritis in a variety of vertebrate hosts. Currently, there is a re-emergence of Cryptosporidium infection; however, no fully effective drug or vaccine is available to treat Cryptosporidiosis. In the present study, to better understand the detailed interaction between the host and Cryptosporidium parvum, a large-scale label-free proteomics study was conducted to characterize the changes to the proteome induced by C. parvum infection. Among 4406 proteins identified, 121 proteins were identified as differentially abundant (> 1.5-fold cutoff, P < 0.05) in C. parvum infected HCT-8 cells compared with uninfected cells. Among them, 67 proteins were upregulated, and 54 proteins were downregulated at 36 h post infection. Analysis of the differentially abundant proteins revealed an interferon-centered immune response of the host cells against C. parvum infection and extensive inhibition of metabolism-related enzymes in the host cells caused by infection. Several proteins were further verified using quantitative real-time reverse transcription polymerase chain reaction and western blotting. This systematic analysis of the proteomics of C. parvum-infected HCT-8 cells identified a wide range of functional proteins that participate in host anti-parasite immunity or act as potential targets during infection, providing new insights into the molecular mechanism of C. parvum infection.
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http://dx.doi.org/10.1371/journal.pntd.0009949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8612570PMC
November 2021

Explore association of genes in PDL1/PD1 pathway to radiotherapy survival benefit based on interaction model strategy.

Radiat Oncol 2021 Nov 18;16(1):223. Epub 2021 Nov 18.

Department of Biostatistics, School of Public Health, Medical College of Soochow University, Suzhou, 215123, China.

Purpose: To explore the association of genes in "PD-L1 expression and PD-1 check point pathway in cancer" to radiotherapy survival benefit.

Methods And Materials: Gene expression data and clinical information of cancers were downloaded from TCGA. Radiotherapy survival benefit was defined based on interaction model. Fast backward multivariate Cox regression was performed using stacking multiple interpolation data to identify radio-sensitive (RS) genes.

Results: Among the 73 genes in PD-L1/PD-1 pathway, we identified 24 RS genes in BRCA data set, 25 RS genes in STAD data set and 20 RS genes in HNSC data set, with some crossover genes. Theoretically, there are two types of RS genes. The expression level of Type I RS genes did not affect patients' overall survival (OS), but when receiving radiotherapy, patients with different expression level of Type I RS genes had varied survival benefit. Oppositely, Type II RS genes affected patients' OS. And when receiving radiotherapy, those with lower OS could benefit a lot. Type II RS genes in BRCA had strong positive correlation and closely biological interactions. When performing cluster analysis using these related Type II RS genes, patients could be divided into RS group and non-RS group in BRCA and METABRIC data sets.

Conclusions: Our study explored potential radio-sensitive biomarkers of several main cancer types in an important tumor immune checkpoint pathway and revealed a strong association between this pathway and radiotherapy survival benefit. New types of RS genes could be identified based on expanded definition to RS genes.
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http://dx.doi.org/10.1186/s13014-021-01951-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8600865PMC
November 2021

Prevalence of Echinococcus Species in Wild Foxes and Stray Dogs in Qinghai Province, China.

Am J Trop Med Hyg 2021 Nov 15. Epub 2021 Nov 15.

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Center for Tropical Diseases, National Center for International Research on Tropical Diseases, Shanghai, China.

Echinococcosis is a zoonotic parasitic disease that is highly endemic to the Qinghai province of China. Limited data are available on the prevalence of the causal pathogen, Echinococcus spp., in definitive hosts in this region. Thus, the aim of this study was to evaluate the prevalence of Echinococcus spp. in wild foxes and stray dogs in Qinghai province. Five hundred and twenty-eight feces from wild foxes and 277 from stray dogs were collected from 11 counties in the Golog, Yushu, and Haixi prefectures and screened for Echinococcus spp. using copro-DNA polymerase chain reaction (PCR). In total, 5.5% of wild foxes and 15.2% of stray dogs tested positive for Echinococcus spp. The prevalence rates of Echinococcus spp. in wild foxes in Golog, Yushu, and Haixi were 7.3%, 5.2%, and 1.9%, respectively. In stray dogs, these rates were 13.3%, 17.3%, and 0%, respectively. Sequencing analysis determined that Echinococcus multilocularis was the most prevalent species, occurring in 4.0% and 12.6% of wild foxes and stray dogs, respectively. Echinococcus shiquicus was observed in 1.5% of wild foxes and 0.7% of stray dogs. Echinococcus granulosus was observed only in wild dogs, with a prevalence rate of 1.8%. To our knowledge, this is the first report on the prevalence of E. shiquicus in dogs in Qinghai province. The current results improve our understanding of the transmission and dissemination of human echinococcosis and suggest that exposure to the eggs of E. multilocularis harbored by wild foxes and stray dogs may pose a great risk of alveolar echinococcosis to humans in Qinghai province.
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http://dx.doi.org/10.4269/ajtmh.21-0622DOI Listing
November 2021

The RNA modification in Echinococcus granulosus cysts revealed by mass spectrometry.

Infect Genet Evol 2021 Oct 26;96:105124. Epub 2021 Oct 26.

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Center for Tropical Diseases; National Center for International Research on Tropical Diseases, Shanghai, China. Electronic address:

RNA modifications, as one of epigenetic mechanisms, are important and conserved mechanisms for maintaining the homeostasis of organisms. Little is known about RNA modifications in Echinococcus granulosus, an obligate parasite that inhabits mammals and gives rise to a huge public health and economic impact. Here, we focused on the RNA modification characteristics of E. granulosus for the first time by using mass spectrometry (UPLC-MS/MS) to qualitatively and quantitatively analyze 47 types of RNA modifications in E. granulosus total RNA. Furthermore, the E. granulosus homologs of writer enzymes preforming RNA modifications were identified, and their gene expression pattern at different developmental stages were analyzed by bioinformatics analysis. Finally, 23 types of RNA modifications were found in E. granulosus cysts total RNA, of which mA, Ψ and mC are the most abundant. The homologs of writer enzymes involved in these modifications were identified in the E. granulosus genome, with the dynamic gene expression during the different parasitic developmental stages. This work confirms that E. granulosus retains the conserved RNA modification mechanism during evolution, suggesting the important role of RNA modification in regulating its development and parasitic process. Moreover, the differences of amino acid sequences of RNA modification writer enzymes between parasite and host make it possible to use these enzymes as the candidate drug targets in the follow-up in-depth researches.
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http://dx.doi.org/10.1016/j.meegid.2021.105124DOI Listing
October 2021

Targeting USP11 may alleviate radiation-induced pulmonary fibrosis by regulating endothelium tight junction.

Int J Radiat Biol 2021 Nov 11:1-11. Epub 2021 Nov 11.

State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, China.

Purpose: Radiation-induced pulmonary fibrosis (RIPF) is a major side effect after radiotherapy for thoracic malignancies. However, rare anti-RIPF therapeutics show definitive effects for treating this disease. Ubiquitin-specific peptidase 11 (USP11) has been reported to promote transforming growth factor β (TGFβ) signaling which plays an essential role underlying RIPF. Herein, we explored the role of USP11 on RIPF.

Materials And Methods: In the present study, USP11-knockout () mice were used to explore the effects of USP11 on RIPF. The lung tissue was obtained after receiving 30 Gy X-ray irradiation. The expression of USP11, TGF-β1, and a-SMA was determined by immunohistochemical and Western Blot, respectively. γ-HAX foci and TUNEL positive cells were detected by fluorescent technique to assess DNA damage and apoptosis. High-throughput proteomic analysis was applied to further explore the related mechanisms. The transwell co-culture method was used to investigate bystander effects in HELF cells induced by irradiated HMEC-1 cells .

Results: Here we found that radiation activated USP11 and . Our results showed that USP11 deficiency effectively decreased serum TGF-β1 level, suppressed α-SMA expression, and mitigated pulmonary fibrosis. In addition, fewer γ-HAX foci and decreased apoptotic cells were identified after irradiation in the primary cells isolated from the lungs of mice. High-throughput proteomics analysis results showed that 22-upregulated and 158-downregulated proteins were identified in the lung tissues of mice after irradiation. Furthermore, gene set enrichment analysis (GSEA) revealed that USP11 deficiency affects the tight junction signaling pathway.

Conclusions: We verified that USP11 deficiency remarkably reinforced tight junction in the endothelial cells and alleviated TGF-β1 to inhibit fibrosis of fibroblast cells. The present study preliminarily showed that USP11-knockout mitigated RIPF via reinforcement endothelial barrier function.
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http://dx.doi.org/10.1080/09553002.2022.1998711DOI Listing
November 2021

MicroRNA‑200c‑3p suppresses intervertebral disc degeneration by targeting RAP2C/ERK signaling.

Mol Med Rep 2021 12 22;24(6). Epub 2021 Oct 22.

Department of Orthopedics, Qingdao No. 6 People's Hospital, Qingdao, Shandong 266033, P.R. China.

Intervertebral disc degeneration (IDD) is a major cause of lower back pain. The high morbidity associated with this disease diminishes the quality of life of those who are affected. MicroRNAs (miRs) play crucial roles in various diseases, including IDD. However, the mechanism via which miR‑200c‑3p plays a role in the development of IDD remains unknown. The present study aimed to investigate the effect of miR‑200c‑3p on the progression of IDD and the underlying mechanism. The expression level of miR‑200c‑3p was evaluated in intervertebral disc tissues from patients with IDD. To construct the IDD cell model, the nucleus pulposus (NP) cells were treated with lipopolysaccharide (LPS) 24 h following transfection with miR‑200c‑3p mimic or inhibitor. A luciferase activity assay was performed, while reverse transcription‑quantitative PCR and western blotting were conducted to determine the RNA and protein expression levels, respectively. The expression level of miR‑200c‑3p in the intervertebral disc tissues of patients with IDD was lower than that of normal subjects. LPS treatment reduced the expression level of miR‑200c‑3p in NP cells. Moreover, miR‑200c‑3p mimic inhibited LPS‑induced NP cell apoptosis. It was found that miR‑200c‑3p attenuated inflammatory cytokine levels and extracellular matrix (ECM) degradation in NP cells. Furthermore, miR‑200c‑3p targeted Ras‑related protein 2C (RAP2C) in NP cells. RAP2C promoted apoptosis, inflammatory cytokine levels and ECM degradation by activating ERK signaling. Knockdown of RAP2C and inhibition of ERK signaling by SCH772984 partially reversed the proinflammatory effect of the miR‑200c‑3p inhibitor on LPS‑treated NP cells. Thus, miR‑200c‑3p inhibits NP cell apoptosis, inflammatory cytokine levels and ECM degradation in IDD by targeting RAP2C/ERK signaling.
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http://dx.doi.org/10.3892/mmr.2021.12505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554383PMC
December 2021

Disulfiram Alone Functions as a Radiosensitizer for Pancreatic Cancer Both and .

Front Oncol 2021 23;11:683695. Epub 2021 Sep 23.

State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, China.

The prognosis of pancreatic cancer remains very poor worldwide, partly due to the lack of specificity of early symptoms and innate resistance to chemo-/radiotherapy. Disulfiram (DSF), an anti-alcoholism drug widely used in the clinic, has been known for decades for its antitumor effects when simultaneously applied with copper ions, including pancreatic cancer. However, controversy still exists in the context of the antitumor effects of DSF alone in pancreatic cancer and related mechanisms, especially in its potential roles as a sensitizer for cancer radiotherapy. In the present study, we focused on whether and how DSF could facilitate ionizing radiation (IR) to eliminate pancreatic cancer. DSF alone significantly suppressed the survival of pancreatic cancer cells after exposure to IR, both and . Additionally, DSF treatment alone caused DNA double-strand breaks (DSBs) and further enhanced IR-induced DSBs in pancreatic cancer cells. In addition, DSF alone boosted IR-induced cell cycle G2/M phase arrest and apoptosis in pancreatic cancer exposed to IR. RNA sequencing and bioinformatics analysis results suggested that DSF could trigger cell adhesion molecule (CAM) signaling, which might be involved in its function in regulating the radiosensitivity of pancreatic cancer cells. In conclusion, we suggest that DSF alone may function as a radiosensitizer for pancreatic cancer, probably by regulating IR-induced DNA damage, cell cycle arrest and apoptosis, at least partially through the CAM signaling pathway.
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http://dx.doi.org/10.3389/fonc.2021.683695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494980PMC
September 2021

NF-E2-Related Factor 2 (Nrf2) Ameliorates Radiation-Induced Skin Injury.

Front Oncol 2021 23;11:680058. Epub 2021 Aug 23.

State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China.

Radiation-induced skin injury (RISI) commonly occur in cancer patients who received radiotherapy and is one of the first clinical symptoms after suffering from nuclear exposure. Oxidative damage is the major causes of RISI. Nuclear factor erythroid 2-related factor 2 (Nrf2) is considered as a key mediator of the cellular antioxidant response. However, whether Nrf2 can alleviate RISI after high-dose irradiation remains unknown. In this study, we demonstrated that Nrf2-deficient ( ) mice were susceptible to high-dose irradiation and adenovirus-mediated overexpression of Nrf2 (ad-Nrf2) protected against radiation in skin cells. Overexpression of Nrf2 attenuated the severity of skin injury after high-dose electron beam irradiation. To uncover the mechanisms of Nrf2 involved in RISI, mRNA sequencing technology was performed to analyze the mRNA expression profiles of Ad-Nrf2 skin cells following radiation. The results revealed that a total of 127 genes were significantly changed, 55 genes were upregulated, and 72 genes were downregulated after Nrf2 overexpression. GSEA showed that Nrf2 was associated with positive regulation of genes involved in the reactive oxygen species pathway after radiation. Taken together, this study illustrated the role of Nrf2 in RISI and provided potentially strategies for ameliorating RISI.
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http://dx.doi.org/10.3389/fonc.2021.680058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461566PMC
August 2021

Granulocytic myeloid-derived suppressor cells inhibit T follicular helper cells during experimental Schistosoma japonicum infection.

Parasit Vectors 2021 Sep 26;14(1):497. Epub 2021 Sep 26.

Key Laboratory of Parasite and Vector Biology, National Health Commission of the People's Republic of China, Shanghai, 200025, China.

Background: CD4 T helper (Th) cells play critical roles in both host humoral and cellular immunity against parasitic infection and in the immunopathology of schistosomiasis. T follicular helper (Tfh) cells are a specialized subset of Th cells involved in immunity against infectious diseases. However, the role of Tfh cells in schistosome infection is not fully understood. In this study, the dynamics and roles of Tfh cell regulation were examined. We demonstrated that granulocytic myeloid-derived suppressor cells (G-MDSC) can suppress the proliferation of Tfh cells.

Methods: The levels of Tfh cells and two other Th cells (Th1, Th2) were quantitated at different Schistosoma japonicum infection times (0,3, 5, 8, 13 weeks) using flow cytometry. The proliferation of Tfh cells stimulated by soluble egg antigen (SEA) and soluble worm antigen (SWA) in vivo and in vitro were analyzed. Tfh cells were co-cultured with MDSC to detect the proliferation of Tfh cells labelled by 5(6)-carboxyfluorescein diacetate N-succinimidyl ester. We dynamically monitored the expression of programmed cell death protein 1 (PD-1) on the surface of Tfh cells and programmed cell death ligand 1 (PD-L1) on the surface of MDSC at different infection times (0, 3, 5, 8 weeks). Naïve CD4 T cells (in Tfh cell differentiation) were co-cultured with G-MDSC or monocytic MDSC in the presence, or in the absence, of PD-L1 blocking antibody.

Results: The proportion of Tfh cells among CD4 T cells increased gradually with time of S. japonicum infection, reaching a peak at 8 weeks, after which it decreased gradually. Both SEA and SWA caused an increase in Tfh cells in vitro and in vivo. It was found that MDSC can suppress the proliferation of Tfh cells. The expression of PD-1 on Tfh cells and PD-L1 from MDSC cells increased with prolongation of the infection cycle. G-MDSC might regulate Tfh cells through the PD-1/PD-L1 pathway.

Conclusions: The reported study not only reveals the dynamics of Tfh cell regulation during S. japonicum infection, but also provides evidence that G-MDSC may regulate Tfh cells by PD-1/PD-L1. This study provides strong evidence for the important role of Tfh cells in the immune response to S. japonicum infection.
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http://dx.doi.org/10.1186/s13071-021-05006-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474882PMC
September 2021

The Critical Role of Tetrahydrobiopterin (BH4) Metabolism in Modulating Radiosensitivity: BH4/NOS Axis as an Angel or a Devil.

Front Oncol 2021 27;11:720632. Epub 2021 Aug 27.

China National Nuclear Corporation 416 Hospital (Second Affiliated Hospital of Chengdu Medical College), Chengdu, China.

Ionizing radiation and radioactive materials have been widely used in industry, medicine, science and military. The efficacy of radiotherapy and adverse effects of normal tissues are closed related to cellular radiosensitivity. Molecular mechanisms underlying radiosensitivity are of significance to tumor cell radiosensitization as well as normal tissue radioprotection. 5,6,7,8-Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide synthases (NOS) and aromatic amino acid hydroxylases, and its biosynthesis involves biosynthesis and a pterin salvage pathway. In this review we overview the role of BH4 metabolism in modulating radiosensitivity. BH4 homeostasis determines the role of NOS, affecting the production of nitric oxide (NO) and oxygen free radicals. Under conditions of oxidative stress, such as UV-radiation and ionizing radiation, BH4 availability is diminished due to its oxidation, which subsequently leads to NOS uncoupling and generation of highly oxidative free radicals. On the other hand, BH4/NOS axis facilitates vascular normalization, a process by which antiangiogenic therapy corrects structural and functional flaws of tumor blood vessels, which enhances radiotherapy efficacy. Therefore, BH4/NOS axis may serve as an angel or a devil in regulating cellular radiosensitivity. Finally, we will address future perspectives, not only from the standpoint of perceived advances in treatment, but also from the potential mechanisms. These advances have demonstrated that it is possible to modulate cellular radiosensitivity through BH4 metabolism.
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http://dx.doi.org/10.3389/fonc.2021.720632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429800PMC
August 2021

Developing ZNF Gene Signatures Predicting Radiosensitivity of Patients with Breast Cancer.

J Oncol 2021 31;2021:9255494. Epub 2021 Aug 31.

Department of Biostatistics, School of Public Health, Medical College of Soochow University, Suzhou, China.

Adjuvant radiotherapy is one of the main treatment methods for breast cancer, but its clinical benefit depends largely on the characteristics of the patient. This study aimed to explore the relationship between the expression of zinc finger (ZNF) gene family proteins and the radiosensitivity of breast cancer patients. Clinical and gene expression data on a total of 976 breast cancer samples were obtained from The Cancer Genome Atlas (TCGA) database. ZNF gene expression was dichotomized into groups with a higher or lower level than the median level of expression. Univariate and multivariate Cox regression analyses were used to evaluate the relationship between ZNF gene expression levels and radiosensitivity. The Molecular Taxonomy Data of the International Federation of Breast Cancer (METABRIC) database was used for validation. The results revealed that 4 ZNF genes were possible radiosensitivity markers. High expression of ZNF644 and low expression levels of the other 3 genes (ZNF341, ZNF541, and ZNF653) were related to the radiosensitivity of breast cancer. Hierarchical cluster, Cox, and CoxBoost analysis based on these 4 ZNF genes indicated that patients with a favorable 4-gene signature had better overall survival on radiotherapy. Thus, this 4-gene signature may have value for selecting those patients most likely to benefit from radiotherapy. ZNF gene clusters could act as radiosensitivity signatures for breast cancer patients and may be involved in determining the radiosensitivity of cancer.
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http://dx.doi.org/10.1155/2021/9255494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423582PMC
August 2021

Development and Validation of a Radiosensitivity Prediction Model for Lower Grade Glioma Based on Spike-and-Slab Lasso.

Front Oncol 2021 30;11:701500. Epub 2021 Jul 30.

Department of Biostatistics, School of Public Health, Medical College of Soochow University, Suzhou, China.

Background And Purpose: Lower grade glioma (LGG) is one of the leading causes of death world worldwide. We attempted to develop and validate a radiosensitivity model for predicting the survival of lower grade glioma by using spike-and-slab lasso Cox model.

Methods: In this research, differentially expressed genes based on tumor microenvironment was obtained to further analysis. Log-rank test was used to identify genes in patients who received radiotherapy and patients who did not receive radiotherapy, respectively. Then, spike-and-slab lasso was performed to select genes in patients who received radiotherapy. Finally, three genes (INA, LEPREL1 and PTCRA) were included in the model. A radiosensitivity-related risk score model was established based on overall rate of TCGA dataset in patients who received radiotherapy. The model was validated in TCGA dataset that PFS as endpoint and two CGGA datasets that OS as endpoint. A novel nomogram integrated risk score with age and tumor grade was developed to predict the OS of LGG patients.

Results: We developed and verified a radiosensitivity-related risk score model. The radiosensitivity-related risk score is served as an independent prognostic indicator. This radiosensitivity-related risk score model has prognostic prediction ability. Moreover, the nomogram integrated risk score with age and tumor grade was established to perform better for predicting 1, 3, 5-year survival rate.

Conclusions: This model can be used by clinicians and researchers to predict patient's survival rates and achieve personalized treatment of LGG.
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http://dx.doi.org/10.3389/fonc.2021.701500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363254PMC
July 2021

Prevalence and genetic characteristics of Blastocystis hominis and Cystoisospora belli in HIV/AIDS patients in Guangxi Zhuang Autonomous Region, China.

Sci Rep 2021 08 5;11(1):15904. Epub 2021 Aug 5.

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research); Key Laboratory of Parasite and Vector Biology, National Health Commission of People's Republic of China, WHO Collaborating Centre for Tropical Diseases, Shanghai, 200025, China.

Blastocystis hominis and Cystoisospora belli are considered to be common opportunistic intestinal protozoa in HIV/AIDS patients. In order to investigate the prevalence and genetic characteristics of B. hominis and C. belli in HIV/AIDS patients, a total of 285 faecal samples were individually collected from HIV/AIDS patients in Guangxi, China. B. hominis and C. belli were investigated by amplifying the barcode region of the SSU rRNA gene and the internal transcribed spacer 1 (ITS-1) region of the rRNA gene, respectively. Chi-square test or Fisher's exact test were conducted to assess the risk factors related to B. hominis and C. belli infection. The prevalence of B. hominis and C. belli was 6.0% (17/285) and 1.1% (3/285) respectively. Four genotypes of B. hominis were detected, with ST3 (n = 8) and ST1 (n = 6) being predominant, followed by ST6 (n = 2) and ST7 (n = 1). Females had a statistically higher prevalence of B. hominis (11.6%) than males (4.2%). The statistical analysis also showed that the prevalence of B. hominis was significantly associated with age group and educational level. Our study provides convincing evidence for the genetic diversity of B. hominis, which indicates its potential zoonotic transmission and is the first report on the molecular characteristics of C. belli in HIV/AIDS patients in China.
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http://dx.doi.org/10.1038/s41598-021-94962-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342556PMC
August 2021

Phthalates in Chinese vehicular environments: Source emissions, concentrations, and human exposure.

Indoor Air 2021 11 21;31(6):2118-2129. Epub 2021 Jul 21.

Department of Energy and Environmental System Engineering, Zhejiang University of Science and Technology, Hangzhou, China.

Phthalates are typical air pollutants in vehicular environment since numerous synthetic materials that might contain phthalates are widely used to fabricate vehicle interiors (e.g., seat cushions, floor mats and dashboards). Hitherto, the importance of phthalate pollution in vehicular environment is not well-recognized because people spend only a small portion (around 8%) of their time in vehicles. In this study, the mass fractions of six phthalates in nine materials commonly used in Chinese vehicles (floor mats and seat cushions) were measured. Two phthalates, di-n-butyl phthalate (DnBP) and di-2-ethylhexyl phthalate (DEHP), were identified in most materials (the other phthalates were not detected). The emission characteristics of DnBP and DEHP from these materials were further investigated. The measured emission parameters were used as input for a mass-transfer model to estimate DnBP and DEHP concentrations in cabin air. Finally, the ratios between human exposures (via inhalation and dermal absorption from the gas phase) in vehicular environment and the total exposures in typical indoor environments (e.g., residences and offices) were estimated to be up to 110% and 20% for DnBP and DEHP, respectively. Based on these results, the vehicular environment might be a considerable site for human exposure to airborne phthalates.
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http://dx.doi.org/10.1111/ina.12910DOI Listing
November 2021

Community Based Assessment of Behavior and Awareness of Risk Factors of Cystic Echinococcosis in Major Cities of Pakistan: A One Health Perspective.

Front Public Health 2021 4;9:648900. Epub 2021 Jun 4.

Key Laboratory of Parasite and Vector Biology, National Health Commission of the People's Republic of China, Shanghai, China.

The parasitic disease, cystic echinococcosis (CE), is a serious health problem in Pakistan. Risk of disease transmission is increased by economic and political instability, poor living conditions, and limited awareness of hygienic practices. The current study aimed to investigate the community perception and awareness regarding the risk factors of CE in Pakistan, from a One Health perspective. We conducted a community-based survey involving 454 participants in the major cities of Pakistan. Quantitative data based on knowledge, attitude, and practices (KAP), the One Health concept, risk factors, and community perception of CE among the general population of the major cities of Pakistan were collected. The questions included those related to knowledge, attitude, practices, One Health concept, risk factors, and community perception. The Chi-squared test was applied to determine the associations regarding KAPs across socio-demographic parameters. KAPs had no significant associations with sociodemographic aspects such as age, sex, religion, ethnicity, education, marital status, occupation, or financial status of the participants. The findings indicated a lack of awareness about CE among the participants. Respondents were unaware of the risk factors and the One Health concept of CE. However, the community attitude and perception were positive toward the control of CE. Illiteracy, deficient sanitation systems and lack of awareness are the contributing factors to CE in Pakistan. It is necessary to make the community aware regarding CE and its importance. Increasing this awareness represents an important step toward the eradication and control of CE.
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http://dx.doi.org/10.3389/fpubh.2021.648900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213035PMC
July 2021

Transplantation of the Stromal Vascular Fraction (SVF) Mitigates Severe Radiation-Induced Skin Injury.

Radiat Res 2021 09;196(3):250-260

The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, 610051, China.

Severe radiation-induced skin injury is a complication of tumor radiotherapy and nuclear accidents. Cell therapy is a potential treatment for radiation-induced skin injury. The stromal vascular fraction (SVF) is a newer material in stem cell therapy that is made up of stem cells harvested from adipose tissue, which has been shown to promote the healing of refractory wounds of different causes. In this study, SVF was isolated from patients with radiation-induced skin injury. Adipose-derived stem cells (ADSCs) accounted for approximately 10% of the SVF by flow cytometry. Compared with the control group of rats, administration with SVF attenuated the skin injury induced by electron beam radiation. The effect of SVF on the human skin fibroblast microenvironment was determined by proteomic profiling of secreted proteins in SVF-co-cultured human skin fibroblast WS1 cells. Results revealed 293 upregulated and 1,481 downregulated proteins in the supernatant of SVF-co-cultured WS1 cells. WS1 co-culture with SVF induced secretion of multiple proteins including collagen and MMP-1. In the clinic, five patients with radiation-induced skin injury were recruited to receive SVF transfer-based therapy, either alone or combined with flap transplantation. Autogenous SVF was isolated and introduced into a multi-needle precision electronic injection device, which automatically and aseptically distributed the SVF to the exact layer of the wound in an accurate amount. After SVF transfer, wound healing clearly improved and pain was significantly relieved. The patients' skin showed satisfactory texture and shape with no further wound recurrence. Our findings suggest that transplantation of SVF could be an effective countermeasure against severe radiation-induced skin injury.
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http://dx.doi.org/10.1667/RADE-20-00156.1DOI Listing
September 2021

Investigation of giardiasis in captive animals in zoological gardens with strain typing of assemblages in China.

Parasitology 2021 09 8;148(11):1360-1365. Epub 2021 Jun 8.

Department of Parasitology, Zunyi Medical University, Zunyi563000, China.

Giardia duodenalis is a common zoonotic intestinal pathogen. It has been increasingly reported in humans and animals; however, genotyping information for G. duodenalis in captive animals is still limited. This study was conducted to assess the prevalence and multilocus genotyping of G. duodenalis in captive animals in zoological gardens in Shanghai, China. A total of 678 fresh fecal samples were randomly collected from captive animals including non-human primates (NHPs) (n = 190), herbivores (n = 190), carnivores (n = 151), birds (n = 138) and reptiles (n = 9) in a zoo and were examined for the presence of G. duodenalis using nested polymerase chain reaction (nested PCR). All G. duodenalis positive samples were assayed with PCR followed by sequencing at β-giardin (bg), glutamate dehydrogenase (gdh) and triose phosphate isomerase (tpi) genes. In this study, 42 specimens (6.2%) were tested G. duodenalis-positive of the 678 fecal samples examined based on a single locus. A total of 30 (4.4%), 30 (4.4%) and 22 (3.2%) specimens were successfully amplified and sequenced at gdh, tpi and bg loci, respectively. Assemblages A and B were identified with assemblage B dominating in NHPs. Sequence analysis demonstrated that one, two and five new isolates were identified at bg, gdh and tpi loci. DNA sequences and new assemblage-subtypes of zoonotic G. duodenalis assemblages A and B were identified in the current study. Our data indicate the occurrence and molecular diversity of G. duodenalis and the potential zoonotic transmission in captive animals in China.
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http://dx.doi.org/10.1017/S0031182021000913DOI Listing
September 2021

Role of lincRNA-Cox2 targeting miR-150 in regulating the viability of chondrocytes in osteoarthritis.

Exp Ther Med 2021 Aug 25;22(2):800. Epub 2021 May 25.

Department of Anesthesiology, Qingdao No. 6 People's Hospital, Qingdao, Shandong 266033, P.R. China.

Osteoarthritis (OA) is a joint disease characterised by progressive cartilage degradation and inflammation, but the detailed pathogenesis of OA remains unclear. The present study aimed to investigate the role of long intergenic non-coding RNA (lincRNA)-Cox2 in OA progression and the potential mechanism. An OA mouse model was used for experiments, and IL-1β-induced injury of mouse chondrocytes was conducted for experiments. Small interfering (si)-Cox2 was transfected into chondrocytes to elucidate the effect of lincRNA-Cox2 on OA. Quantitative reverse transcription PCR assays were conducted to detect the expression of lincRNA-Cox2 and microRNA (miR)-150. Cell proliferation and apoptosis were analysed based on an MTT assay and annexin V/propidium iodide staining, respectively. Western blotting was performed to evaluate the protein expression levels of Ki-67, PCNA, Bax, cleaved (c)-Caspase-3, c-Caspase-9 and Wnt/β-catenin pathway-associated proteins in chondrocytes. High levels of lincRNA-Cox2 were observed in cartilage tissues of the OA mouse model . In the experiments, the expression of lincRNA-Cox2 was increased in IL-1β-treated chondrocytes. Knockdown of lincRNA-Cox2 promoted the proliferation and inhibited the apoptosis of chondrocytes. Mechanistically, lincRNA-Cox2 was found to directly target miR-150, acting as a competing endogenous RNA, and the effect of si-Cox2 on the proliferation and apoptosis of chondrocytes was reversed by miR-150 inhibitors. Moreover, lincRNA-Cox2 activated the Wnt/β-catenin pathway to regulate chondrocyte proliferation and apoptosis. The present study demonstrated that silencing lincRNA-Cox2 expression plays a protective role in OA by enhancing the proliferation and suppressing the apoptosis of chondrocytes, which is related to increased miR-150 expression and activation of the Wnt/β-catenin pathway.
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http://dx.doi.org/10.3892/etm.2021.10232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170664PMC
August 2021

Comparative Proteomics Analysis for Elucidating the Interaction Between Host Cells and .

Front Cell Infect Microbiol 2021 13;11:643001. Epub 2021 May 13.

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), National Health Commission of People's Republic of China Key Laboratory of Parasite and Vector Biology, World Health Organization Collaborating Centre for Tropical Diseases, Shanghai, China.

, a representative model organism belonging to the phylum Apicomplexa, can infect almost all warm-blooded organisms, including humans. The invasion of host cells host-parasite interaction is the key step for to complete its life cycle. Herein we performed tandem mass tag analysis to investigate global proteomic changes in host cells (human foreskin fibroblasts, HFFs) [HFFs infected with (HT) . HFFs (H)] and [HT . (T)] during intracellular infection. Overall, 3477 and 1434 proteins were quantified, of which 375 and 1099 proteins were differentially expressed (adjusted p-value < 0.05 and >1.5 or <0.67-fold change) in host cells and , respectively. invasion relies on the secretion of numerous secretory proteins, which originate from three secretory organelles: micronemes, rhoptries, and dense granules. In the HT . T group, few secretory proteins were upregulated, such as microneme proteins (MICs: MIC6, MIC10), rhoptry bulb proteins (ROPs: ROP5, ROP17), and dense granule proteins (GRAs: GRA4, GRA5, GRA12). In contrast, dozens of known secretory proteins were significantly downregulated in -infected HFFs. In HFFs, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed a large number of differentially expressed proteins (DEPs) enriched in metabolic processes and immune-associated signaling pathways, such as NF-κB, cAMP, and Rap1 signaling pathways. Further, in case of , DEPs were involved in ribosome biogenesis, citrate cycle, and galactose metabolism, indicating that cell biosynthesis and metabolism of were altered after host cell invasion. These findings reveal novel modifications in the proteome of host cells as well as , helping us better understand the mechanisms underlying host-parasite interaction.
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http://dx.doi.org/10.3389/fcimb.2021.643001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158437PMC
July 2021

Epidemiological analysis of cystic echinococcosis and alveolar echinococcosis in an extremely high prevalence region: Population-based survey and host animal monitoring in Shiqu County, China.

Acta Trop 2021 Sep 25;221:105982. Epub 2021 May 25.

Sichuan Center for Animal Disease Control and Prevention, Chengdu, China.

Echinococcosis is the most common parasitic disease in the Tibetan Plateau, placing a large disease burden on the local population. Shiqu County, located in western Sichuan Tibetan region, had a particularly high prevalence rate of cystic echinococcosis (CE) and alveolar echinococcosis (AE) in previous surveys. From 2015 to 2018, a population-based field survey was conducted to explore the epidemic situation. Epidemiological features were examined through demographic analysis and mapping. In addition, the infection prevalence of Echinococcus in dogs was also investigated and mapped by spatial autoregression. A total of 84,768 people were screened by abdominal ultrasound inspection, and 2,341 CE and 3,930 AE cases were detected, with a corresponding prevalence of 2.76% and 4.64%, respectively. This made Shiqu County one of the most severe echinococcosis endemic regions in the world, especially with regard to AE. The cases were not evenly distributed among towns: particularly, the AE rates in the northwest towns were very high and closely related to the infection rate of neighboring host animals. Simultaneously, a comprehensive prevention project including patient treatment and host management was conducted and achieved preliminary success in source control. According to feces monitoring findings, the infection rate of dogs declined from 26.38% in early 2016 to 3.71% in 2018. Combined with host animal distribution data at the town level, the predicted risk ranks were categorized by risk index and mapped to guide further control operations.
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http://dx.doi.org/10.1016/j.actatropica.2021.105982DOI Listing
September 2021

Higher frequency of circulating Vδ1 γδT cells in patients with advanced schistosomiasis.

Parasite Immunol 2021 10 21;43(10-11):e12871. Epub 2021 Jul 21.

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), Key Laboratory of Parasite and Vector Biology, National Health Commission of People's Republic of China, WHO Collaborating Center for Tropical Diseases, Shanghai, China.

Gamma-delta (γδ) T cells are the bridge between natural and adaptive immunity. In the present study, peripheral blood was collected from 13 patients with advanced schistosomiasis (schistosomiasis group) and 13 uninfected people (control group) to investigate the γδ T cells and their subtypes in human schistosomiasis. Compared with the control group, the proportion of Vδ1 cells and CD27 Vδ1 cells in the schistosomiasis group increased significantly, while CD27 cells and CD27 Vδ1 cells decreased. Only the level of IL-17A differed between the groups, being significantly decreased in the schistosomiasis group. In the schistosomiasis group, there were no correlations between the liver fibrosis and subsets of γδ T cells, or the level of cytokines. Additionally, the level of IL-17A correlated positively with the proportion of CD27 Vδ1 cells. Thus, there was a higher frequency of circulating Vδ1 γδT cells in patients with advanced schistosomiasis. The decreased IL-17A might be related to the reduction in CD27 Vδ1 cell.
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http://dx.doi.org/10.1111/pim.12871DOI Listing
October 2021

Risk Factors for Infection in Residents of Binyang, Guangxi: A Cross-Sectional and Logistic Analysis Study.

Front Public Health 2021 5;9:588325. Epub 2021 May 5.

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, Shanghai, China.

Clonorchiasis is a serious food-borne parasitic disease caused by infection. , a major fish-borne trematode, is a known causative agent of cholangiocarcinoma. The risk factors for infection include individual eating behaviors and environmental factors. In this study, we evaluated the infection rate and the associated risk factors among residents in Binyang County, Guangxi, China. In 2016 and 2017, five villages from Binyang, Guangxi were selected by multistage cluster random sampling for a cross-sectional study. A modified Kato-Katz thick smear method was used to examine eggs in fecal samples in triplicate (three smears for each sample). Both uni-variate and multi-variate logistic regression analyses were carried out to identify the risk factors for infection. A total of 1,977 fecal samples were collected from villagers in the investigated areas. The overall infection rates of in Binyang County was 20.49% (405/1,977). The mean age of participants was 39.42 ± 23.48 (range: 3-89 years old), and the highest infection rate (33.72%) was seen in the age group of 40-49 years old, followed by those aged 50-59 (31.83%). Multi-variate logistic regression analysis showed that higher infection rates were significantly associated with males ( = 6.51, = 4.67-9.08), Zhuang ( = 2.41, = 1.62-3.59), ages ( = 33.51, = 10.13-110.86), frequency of raw fresh fish consumption ( = 14.56, = 9.80-21.63), and close contact with cats and dogs ( = 1.53, = 1.02-2.30). Occupations and education levels showed no significant association with infection ( > 0.05). High levels of infection were observed among residents in Binyang County, Guangxi. Intervention strategies should be strengthened among the investigated population at high risk, such as males, Zhuang and older individuals, especially those who frequently eat raw fresh fish. In addition, the individuals contacting with cats and/or dogs were observed to have significantly higher infection rate of than those having no contact with cats and dogs. The association between contacting with cats and/or dogs and infection needs to be explored and confirmed in the future study by more epidemiological investigations of human infection from different areas.
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http://dx.doi.org/10.3389/fpubh.2021.588325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131673PMC
May 2021

Haplotype comparisons of mitochondrial gene sequences (1, , 1) among Pakistan and its neighbouring countries.

Parasitology 2021 08 26;148(9):1019-1029. Epub 2021 Apr 26.

National Institute of Parasitic Diseases, Chinese Centre for Disease Control and Prevention (Chinese Center for Tropical Diseases Research); Key Laboratory of Parasite and Vector Biology; National Health Commission of the People's Republic of China; WHO Collaborating Centre for Tropical Diseases; National Center for International Research on Tropical Diseases; Shanghai; China.

Echinococcus granulosus sensu lato (s.l.) is a zoonotic parasite that causes cystic echinococcosis (CE) in humans. However, E. granulosus sensu stricto (s.s.) is considered the predominant species in CE infections worldwide. According to the population genetic diversity and structure of E. granulosus s.l., gene flow can explain the parasite drift among the neighbouring countries of Pakistan. The mitochondrial (mt) co1 (n = 47), nadh1 (n = 37) and cytb (n = 35) nucleotide sequences of E. granulosus s.l. isolates from Pakistan, Iran, China and India were retrieved from the National Centre for Biotechnology Information database to determine the genealogical relationships. The sequences were grouped as the mt-co1 (genotypes G1 and G3, G6-G7), mt-cytb (genotypes G1 and G3), and mt-nadh1(genotypes G1 and G3). The data were analysed using bioinformatic tools. A total of 19 polymorphic sites for the mt-co1 sequence (374 bp) were observed of which 31.6% (6/19) were parsimony-informative sites. Unique singleton haplotypes within the E. granulosus s.s. haplotype network based on the mt-co1 gene were highly prevalent (68.4%; 13/19) in Pakistani isolates followed by Chinese, Indian and Iranian isolates; four polymorphic sites were detected in the E. canadensis (G6/G7). In E. canadensis mt-co1 haplotype network, 75% (3/4) unique singleton haplotypes were from the Iranian isolates. Twelve polymorphic sites were found using the mt-cytb sequence (547 bp); 25% (3/12) were parsimony-informative and there were 66.7% (8/12) unique singleton haplotypes within the mt-cytb haplotype network in E. granulosus s.s. with the most reported from Pakistan followed by Iran and China. 20 polymorphic sites were detected in E. granulosus s.s. mt-nadh1 sequences (743 bp); 20% (4/20) were parsimony-informative. There were 66.7% (8/12) main single haplotypes within the mt-nadh1 haplotype network, with the most reported from Pakistan followed by that from India, Iran and China. The sequence analyses show low nucleotide diversity and high haplotype diversity in general.
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http://dx.doi.org/10.1017/S0031182021000688DOI Listing
August 2021

Developing a lncRNA Signature to Predict the Radiotherapy Response of Lower-Grade Gliomas Using Co-expression and ceRNA Network Analysis.

Front Oncol 2021 9;11:622880. Epub 2021 Mar 9.

Department of Biostatistics, School of Public Health, Medical College of Soochow University, Suzhou, China.

Background: Lower-grade glioma (LGG) is a type of central nervous system tumor that includes WHO grade II and grade III gliomas. Despite developments in medical science and technology and the availability of several treatment options, the management of LGG warrants further research. Surgical treatment for LGG treatment poses a challenge owing to its often inaccessible locations in the brain. Although radiation therapy (RT) is the most important approach in this condition and offers more advantages compared to surgery and chemotherapy, it is associated with certain limitations. Responses can vary from individual to individual based on genetic differences. The relationship between non-coding RNA and the response to radiation therapy, especially at the molecular level, is still undefined.

Methods: In this study, using The Cancer Genome Atlas dataset and bioinformatics, the gene co-expression network that is involved in the response to radiation therapy in lower-grade gliomas was determined, and the ceRNA network of radiotherapy response was constructed based on three databases of RNA interaction. Next, survival analysis was performed for hub genes in the co-expression network, and the high-efficiency biomarkers that could predict the prognosis of patients with LGG undergoing radiotherapy was identified.

Results: We found that some modules in the co-expression network were related to the radiotherapy responses in patients with LGG. Based on the genes in those modules and the three databases, we constructed a ceRNA network for the regulation of radiotherapy responses in LGG. We identified the hub genes and found that the long non-coding RNA, DRAIC, is a potential molecular biomarker to predict the prognosis of radiotherapy in LGG.
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http://dx.doi.org/10.3389/fonc.2021.622880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985253PMC
March 2021

Genotyping and zoonotic potential of Cryptosporidium and Enterocytozoon bieneusi in pigs transported across regions in China.

Microb Pathog 2021 May 6;154:104823. Epub 2021 Mar 6.

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, WHO Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases, Ministry of Science and Technology, Key Laboratory of Parasite and Vector Biology, Ministry of Health, Shanghai, 200025, PR China. Electronic address:

Cryptosporidium spp. and Enterocytozoon bieneusi are common and important enteric parasites that can infect humans and animals, causing diarrhoea and systemic diseases. The objectives of the present study were to examine the prevalence and genetic variations of Cryptosporidium and E. bieneusi in pigs transferred from northeastern China to Ningbo city in Zhejiang Province. Cryptosporidium spp. was detected in 0.9% (2/216) of these samples and belonged to the zoonotic species Cryptosporidium parvum. A high E. bieneusi infection rate (25.0%, 54/216) was observed in this study, with 7 possible novel ITS genotypes (JLNB-1 to JLNB-7) and 10 known genotypes (EbpA, CM11, H, CM6, pigEBITS1, EbpC, CS-4, pigEBITS5, CHS5, and Henan-Ⅳ) identified, and zoonotic EbpA was the dominant genotype. Genotypes H and pigEBITS1 were reported for the first time in pigs in China. Phylogenetic analysis indicated that all the genotypes found in these samples belonged to zoonotic group 1. These findings indicated the potential threat of Cryptosporidium and E. bieneusi to humans or the environment during cross-regional transportation. An effective management control system should be built to avoid parasitic transmission as well as other animal diseases while travelling across different regions. In further studies, attention should be given to the transmission routes and the role of pigs as a potential source of human Cryptosporidium and E. bieneusi infections in China.
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http://dx.doi.org/10.1016/j.micpath.2021.104823DOI Listing
May 2021

Assessing and controlling infection risk with Wells-Riley model and spatial flow impact factor (SFIF).

Sustain Cities Soc 2021 Apr 16;67:102719. Epub 2021 Jan 16.

Department of Building Science, Tsinghua University, Beijing, China.

The ongoing COVID-19 epidemic has spread worldwide since December 2019. Effective use of engineering controls can prevent its spread and thereby reduce its impact. As airborne transmission is an important mode of infectious respiratory disease transmission, mathematical models of airborne infection are needed to develop effective engineering control. We developed a new approach to obtain the spatial distribution for the probability of infection (PI) by combining the spatial flow impact factor (SFIF) method with the Wells-Riley model. Our method can be combined with the anti-problem approach, in order to determine the optimized arrangement of people and/or air purifiers in a confined space beyond the ability of previous methods. This method was validated by a CFD-integrated method, and an illustrative example is presented. We think our method can be helpful in controlling infection risk and making the best use of the space and equipment in built environments, which is important for preventing the spread of COVID-19 and other infectious respiratory diseases, and promoting the development of sustainable cities and society.
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http://dx.doi.org/10.1016/j.scs.2021.102719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834120PMC
April 2021

Alteration of the fecal microbiota in Chinese patients with Schistosoma japonicum infection.

Parasite 2021 8;28. Epub 2021 Jan 8.

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, 200025 Shanghai, PR China - Chinese Center for Tropical Diseases Research, 200025 Shanghai, PR China - World Health Organization Collaborating Centre for Tropical Diseases, 200025 Shanghai, PR China - Key Laboratory of Parasite and Vector Biology, National Health Commission of the People's Republic of China, 200025 Shanghai, PR China.

Schistosoma japonicum infection causes pathological injury to the host. Multiple studies have shown that intestinal helminth infection causes dysbiosis for the gut microbial community and impacts host immunology. However, the effect of acute S. japonicum infection on the gut microbiome structure (abundance and diversity) is still unclear. We collected fecal samples from healthy and infected patients from a single hospital in Hunan Province, China. The bacterial community was analyzed using 16S ribosomal RNA gene sequencing of the V4 hypervariable region using the HiSeq platform. Compared with healthy subjects, infected patients exhibited an increase in relative abundance of the TM7 phylum. At the genus level, there were seven differentially abundant genera between groups. The most significant finding was a Bacteroides enterotype in patients with acute schistosomiasis. These results suggest that S. japonicum infection has a significant effect on microbiome composition characterized by a higher abundance of the TM7 phylum and development of a Bacteroides enterotype.
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http://dx.doi.org/10.1051/parasite/2020074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792497PMC
February 2021

Individualized prognostic signature for pancreatic carcinoma validated by integrating immune-related gene pairs (IRGPs).

Bioengineered 2021 12;12(1):88-95

Department of General Surgery, Second Affiliated Hospital of Soochow University , Souzhou Jiangsu, China.

Increasingly attention is being given to immune molecules in pancreatic cancer. The purpose of this study was to understand the potential clinical application of immune-regulated genes (IRGs) in the stratification of prognosis and to facilitate the development of personalized prognostic information for pancreatic cancer patients. We systematically used public data to comprehensively analyze immune-regulated gene pair (IRGP) expression profiles and clinical data. In our study, IRGP signature was identified to predict the overall survival (OS) of pancreatic cancer patients. We suggested that immune genes are enriched in different risk groups. In the high-risk group, M1 macrophages and resting NK cells were significantly enriched, while the percentages of naïve B cells, resting dendritic cells, CD8 T cells and regulatory T cells (Tregs) were significantly higher in the low-risk group, and we verified these results with immunohistochemical experiments. Gene ontology (GO) analysis confirmed that the IRGP index (IRGPI) signature genes in the cohort were mostly party to sensory perception of a chemical stimulus and the adaptive immune response. The identification of these pathways provides a basis for studying the molecular mechanisms of IRGPI signaling to predict the prognosis of pancreatic cancer. Our study effectively constructed a robust IRGP signature with prognostic value for pancreatic cancer, presenting a conceivable method for deciding on a preoperative treatment.
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http://dx.doi.org/10.1080/21655979.2020.1860493DOI Listing
December 2021

Functional Inhibition of Natural Killer Cells in a BALB/c Mouse Model of Liver Fibrosis Induced by Infection.

Front Cell Infect Microbiol 2020 19;10:598987. Epub 2020 Nov 19.

Key Laboratory of Parasite and Vector Biology, National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, WHO Collaborating Center for Tropical Diseases, Shanghai, China.

Background And Aims: Schistosomiasis japonica is a widespread human zoonotic disease, and in China, there are many patients with schistosomiasis suffering from liver fibrosis. Many studies have shown that natural killer (NK) cells could reduce the progression of hepatic fibrosis by directly killing hepatic stellate cells (HSCs). However, NK cells could not inhibit the progress of liver fibrosis induced by infection. We aimed to investigate the function of NK cells in schistosomiasis.

Methods: BALB/c mice were infected with S. japonicum cercariae. The receptors and their proportions expressed on NK cells in the liver and spleen from infected mice were detected using flow cytometry. Levels of IFN-γ, perforin, and granzyme of NK cells, and collagen I, III, and α-SMA of hepatic tissue, were detected using quantitative real-time PCR. Changes in cytokine levels in sera were detected using a cytometric bead array. Liver fibrosis was evaluated using hematoxylin and eosin and Masson staining. NK function in the schistosomiasis model was analyzed.

Results: From 2 to 4 weeks post-infection, NK cells were activated, with significantly increased levels of effector molecules (IFN-γ, perforin, and granzyme) that peaked at 4 weeks after infection. The proportion of NK cells increased in the liver and spleen from 6 to 10 weeks post-infection. However, the function of NK cells was inhibited from 6 to 10 weeks post-infection with significantly decreased levels of activated receptors (AR), inhibitory receptors (IR), and effector molecules. The levels of IFN-γ, IL-12, and IL-6 in mouse serum peaked at 6 weeks post-infection, and IL-10 and IL-21 levels peaked at 8 weeks post-infection. Hepatic fibrosis markers increased significantly at 6 weeks after infection.

Conclusion: Our study suggested that NK cells were activated from 2 to 4 weeks post-infection and participated in inflammation in the mouse model. After the S. japonicum laid their eggs, NK cells became inhibited, with decreased levels of both activating and inhibitory NK cell receptors, as well as cytotoxic molecules. In addition, liver fibrosis formed. In mice infected with S. japonicum, the process of liver fibrosis might be alleviated by removing the functional inhibition of NK cells.
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http://dx.doi.org/10.3389/fcimb.2020.598987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710793PMC
June 2021

Identification of Uncommon (a Novel Subtype XVcA2G1c) and as Well as Common Assemblages A and B in Humans in Myanmar.

Front Cell Infect Microbiol 2020 25;10:614053. Epub 2020 Nov 25.

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, WHO Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases, Ministry of Science and Technology, Key Laboratory of Parasite and Vector Biology, MOH, Shanghai, China.

and are two important zoonotic intestinal protozoa responsible for diarrheal diseases in humans and animals worldwide. Feces from infected hosts, water and food contaminated by oocysts and cysts as well as predictors such as poverty have been involved in their transmission. Myanmar is one of the world's most impoverished countries. To date, there are few epidemiological studies of and in humans. To understand the prevalence and genetic characterization of spp. and in humans in Myanmar, a molecular epidemiological investigation of the two protozoa was conducted in four villages of Shan State. 172 fecal specimens were collected from Wa people (one each) and identified for the presence of spp. and by sequence analysis of their respective small subunit ribosomal RNA genes. 1.74% of investigated people were infected with spp.- (n = 2) and (n = 1) while 11.05% infected with -assemblages A (n = 6) and B (n = 13). By sequence analysis of 60-kDa glycoprotein gene, the isolate belonged to a novel subtype XVcA2G1c. DNA preparations positive for were further subtyped. Five of them were amplified and sequenced successfully: different assemblage B sequences (n = 2) at the triosephosphate isomerase (tpi) locus; sub-assemblage AII sequence (n = 1) and identical assemblage B sequences (n = 2) at the β-giardin (bg) locus. This is the first molecular epidemiological study of spp. and in humans in Myanmar at both genotype and subtype levels. Due to unclear transmission patterns and dynamics of spp. and , future research effort should focus on molecular epidemiological investigations of the two parasites in humans and animals living in close contact in the investigated areas, even in whole Myanmar. These data will aid in making efficient control strategies to intervene with and prevent occurrence of both diseases.
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http://dx.doi.org/10.3389/fcimb.2020.614053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724083PMC
June 2021
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