Publications by authors named "Xinmei Huang"

50 Publications

Transcriptome analysis reveals new insight of duck Tembusu virus (DTMUV)-infected DF-1 cells.

Res Vet Sci 2021 Jul 29;137:150-158. Epub 2021 Apr 29.

Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Diagnosis, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, Nanjing, 210014, China.

Duck Tembusu virus (DTMUV) is a newly emerging pathogenic flavivirus that has caused huge economic losses to the duck industry in China since 2010. Moreover, the infection has spread rapidly, resulted in a potential public health concern. To improve our understanding of the host cellular responses to virus infection and the pathogenesis of DTMUV infection, we used RNA-Seq to detect the gene changes in DF-1 cells infected and mock-infected with DTMUV. A total of 663 differentially-expressed genes (DEGs) were identified in DTMUV-infected compared with mock-infected DF-1 cells at 24 h post-infection (hpi), among which 590 were up regulated and 73 were down regulated. Gene Ontology analysis indicated that the DEGs were mainly involved in cellular process, immune system processes, metabolic processes, and signal-organism process. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the DEGs were mainly involved in several signaling pathways such as Toll-like receptor signaling, Jak-STAT signaling, RIG-I-like receptor signaling and AGE-RAGE signaling pathway. Moreover, some selected DEGs were further confirmed by real-time PCR and the results were consistent with the sequencing data. To our knowledge, this study is the first to analyze the transcriptomic change in DF-1 cells following DTMUV infection. We believe that our research provides useful information in better understanding the host response to DTMUV infection and the inherent mechanism of DTMUV replication and pathogenicity.
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http://dx.doi.org/10.1016/j.rvsc.2021.04.028DOI Listing
July 2021

Impact of chronic respiratory diseases on re-intubation rate in critically ill patients: a cohort study.

Sci Rep 2021 Apr 21;11(1):8663. Epub 2021 Apr 21.

Department of Intensive Care, Zhejiang Hospital, No. 12, Lingyin Road, Hangzhou, 322100, Zhejiang, People's Republic of China.

Chronic respiratory diseases' (CRDs) impact on re-intubation rate remains unclear. We investigated the association between these factors in mechanically ventilated patients. Data were extracted from the freely available online Medical Information Mart for Intensive Care III database. CRDs were defined according to ICD-9 codes. Generalised linear regression and propensity score matching were performed. Of 13,132 patients, 7.9% required re-intubation. Patients with chronic obstructive pulmonary disease (COPD) had higher re-intubation (OR 2.48, 95% CI 1.83-3.33) and mortality rates (OR 1.64, 95% CI 1.15-2.34) than those without. Patients with asthma had a lower mortality rate (OR 0.63, 95% CI 0.43-0.92) but a similar re-intubation rate to those of patients without. These findings remained stable after propensity score matching and bootstrapping analysis. The association of COPD with re-intubation was significantly stronger in patients with high oxygen-partial pressure (PaO) or mild disease severity but was independent of carbon dioxide partial pressure. Corticosteroid use was associated with increased re-intubation rates in subgroups without CRDs (OR 1.77-1.99, p < 0.001) but not in subgroups with CRDs. COPD patients with high post-extubation PaO or mild disease severity should be carefully monitored as they have higher re-intubation and mortality rates.
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http://dx.doi.org/10.1038/s41598-021-88007-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060362PMC
April 2021

Impact of Fluid Balance on Mortality Is Mediated by Fluid Accumulation Index in Sepsis: A Cohort Study.

J Intensive Care Med 2020 Oct 28:885066620960626. Epub 2020 Oct 28.

Department of Intensive Care Unit, Zhejiang Hospital, Hangzhou, Zhejiang, People's Republic of China.

Fluid balance (FB) is associated with poor sepsis outcomes; however, it cannot accurately reflect the dynamic fluid accumulation status. Here, we explored a new index, the FB to fluid intake ratio (FB/FI), for evaluating dynamic fluid accumulation in sepsis. FB/FI values within 48 hours were recorded. Their association with in-hospital mortality was investigated using logistic regression and mediation analyses of data from 7,839 patients. In extended logistic models, a linear association was found between FB and mortality (odds ratio [OR]: 1.05-1.08, p < 0.001). However, this association became non-significant after the adjustment of FB/FI (OR: 1.00, 95% confidence interval [CI]: 0.98-1.02). For FB/FI and mortality, a cut-off value of 0.25 was defined. In the spline function logistic model, FB/FI > 0.25 was significantly associated with increased mortality (OR: 4.46, 95% CI: 2.92-6.80), whereas FB/FI ≤ 0.25 was not. For the FB/FI > 0.25 subgroup, mediation analysis was used to clarify the relationship between FB, FB/FI, and mortality. We observed that the direct effect of FB was non-significant (adjusted coefficient: -0.001, 95% CI: -0.005 to 0.002) while the indirect effect was significant (adjusted coefficient: 0.009, 95% CI: 0.006-0.011). In the FB/FI ≤ 0.25 subgroup, both the FB volume (0.9 ± 0.7 vs. -2.0 ± 1.9, p < 0.001) and the FB/FI ratio (0.14 ± 0.07 vs. -0.77 ± 1.60, p < 0.001) were significantly higher in patients with FB > 0 than those with FB ≤ 0. However, both the crude and adjusted comparisons of hospital mortality were non-significant. Similar associations were observed in septic shock patients. FB/FI > 0.25 is a significant risk factor for mortality in sepsis, while FB/FI ≤ 0.25 is not. The association between FB and mortality is completely mediated by this new fluid accumulation index. More comprehensive indices are required for evaluating dynamic fluid status in sepsis.
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http://dx.doi.org/10.1177/0885066620960626DOI Listing
October 2020

Analysis of the microRNA expression profiles of chicken dendritic cells in response to H9N2 avian influenza virus infection.

Vet Res 2020 Oct 17;51(1):132. Epub 2020 Oct 17.

Key Laboratory of Veterinary Biological Engineering and Technology of Ministry of Agriculture, National Center for Engineering Research of Veterinary Bio-products, Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, 50 Zhongling Street, Nanjing, 210014, Jiangsu, China.

MicroRNA (miRNA) plays a key role in virus-host interactions. Here, we employed deep sequencing technology to determine cellular miRNA expression profiles in chicken dendritic cells infected with H9N2 avian influenza virus (AIV). A total of 66 known and 36 novel miRNAs were differently expressed upon H9N2 infection, including 72 up-regulated and 30 down-regulated miRNAs. Functional analysis showed that the predicted targets of these miRNAs were significantly enriched in several pathways including endocytosis, notch, lysosome, p53, RIG-I-like and NOD-like receptor signaling pathways. These data provide valuable information for further investigating the roles of miRNA in AIV pathogenesis and host defense response.
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http://dx.doi.org/10.1186/s13567-020-00856-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568386PMC
October 2020

Cancer-driven IgG promotes the development of prostate cancer though the SOX2-CIgG pathway.

Prostate 2020 09 6;80(13):1134-1144. Epub 2020 Jul 6.

Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, China.

Background: Although androgen deprivation therapy (ADT) is the initial treatment strategy for prostate cancer (PCa), recurrent castration-resistant prostate cancer (CRPC) eventually ensues. In this study, cancer-derived immunoglobulin G (CIgG) is found to be induced after ADT, identifying CIgG as a potential CRPC driver gene.

Methods: The expression of CIgG and its clinical significance in PCa tissue was analyzed by The Cancer Genome Atlas database and immunohistochemistry. Subsequently, the sequence features of prostate cell line VHDJH rearrangements were analyzed. We also assessed the effect of CIgG on the migratory, invasive and proliferative abilities of PCa cells in vitro and vivo. Suspended microsphere, colony formation and drug-resistant assays were performed using PC3 cells with high CIgG expression (CIgG ) and low CIgG expression (CIgG ), and A nonobese diabetic/severe combined immunodeficiency mouse tumor xenograft model was developed for the study of the tumorigenic effects of the different cell populations. The SOX2-CIgG signaling pathway was validated by immunohistochemistry, immunofluorescence, quantitative reverse transcription-polymerase chain reaction, Western blot, luciferase, and chromatin immunoprecipitation assays and bioinformatics analyses. Finally, we investigated the effect of RP215 inhibition on the progression of PCa in vivo using a Babl/c nude mouse xenograft model.

Results: CIgG is frequently expressed in PCa and associated with clinicopathological characteristics, moreover, CIgG transcripts with unique patterns of VHDJH rearrangements are found in PCa cells. Functional analyses identified that CIgG was induced by ADT and upregulated by SOX2 (SRY (sex determining region Y)-box 2) in PCa, promoting the development of PCa. In addition, our findings underscore a novel role of CIgG signaling in the maintenance of stemness and the progression of cancer through mitogen activated protein kinase/extracellular-signal-regulated kinase and AKT in PCa. In vivo experiments further demonstrated that depleting CIgG significantly suppressed the growth of PCa cell xenografts. Furthermore, a CIgG monoclonal antibody named RP215 exhibits tumor inhibitory effect as well.

Conclusion: Our data suggests that CIgG could be a driver of PCa development, and that targeting the SOX2-CIgG axis may therefore inhibit PCa development after ADT.
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http://dx.doi.org/10.1002/pros.24042DOI Listing
September 2020

Low Serum IL-17A in Pregnancy During Second Trimester Is Associated With an Increased Risk of Subclinical Hypothyroidism.

Front Endocrinol (Lausanne) 2020 14;11:298. Epub 2020 May 14.

Department of Endocrinology, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China.

Interleukin-17A (IL-17A) has a role in sustaining normal pregnancy. IL-17A is also associated with thyroid autoimmunity during pregnancy. This study sought to investigate whether IL-17A is a risk factor for thyroid dysfunction during pregnancy in women negative for thyroid autoantibodies. The study comprised 216 pregnant women with negative thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) during the second trimester who provided blood samples for serum IL-17A, thyroid autoantibodies and thyroid function tests. To further evaluate the ratio of CD4+IL-17A+ Th17 cells, we collected peripheral blood from 26 women with thyroid-stimulating hormone (TSH) levels ≤ 2.5 mIU/L and 26 pregnancy-week matched women with TSH levels >2.5 mIU/L, along with samples from 20 women with TSH levels ≤ 4 mIU/L and 20 pregnancy-week matched women with TSH levels >4 mIU/L. The serum IL-17A levels and ratios of CD4+IL-17A+ cells were significantly lower in women with TSH > 2.5 mIU/L than in those with TSH ≤ 2.5 mIU/L (both < 0.01). Similar lower differences were noted in women with TSH > 4 mIU/L than in those with TSH ≤ 4 mIU/L (both < 0.01). Moreover, serum TSH correlated negatively with IL-17A levels (β = -0.195, = 0.004), but positively with the week of gestation (β = 0.284, < 0.001). Logistic regression indicated that a lower serum IL-17A level was a risk factor for TSH > 2.5 mIU/L [OR = 0.453 (0.298-0.689), = 0.000] and TSH > 4.0 mIU/L [OR = 0.588 (0.385-0.899), = 0.013]. A low serum IL-17A level during the second trimester is associated with an increased risk of TSH > 2.5 mIU/L and subclinical hypothyroidism.
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http://dx.doi.org/10.3389/fendo.2020.00298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239996PMC
May 2021

Peptide inhibitors of tembusu virus infection derived from the envelope protein.

Vet Microbiol 2020 Jun 7;245:108708. Epub 2020 May 7.

College of Animal Science and Technology, Shandong Agricultural University, Tai'an, Shandong province, PR China; Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Tai'an, Shandong, PR China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Tai'an, Shandong, PR China. Electronic address:

The outbreak and spread of Tembusu virus (TMUV) has caused very large losses in the waterfowl-breeding industry since 2010. The viral envelope (E) protein, the principal surface protein of viral particles, plays a vital role in viral entry and fusion. In this study, two peptides derived from domain II (DII) and the stem of the TMUV envelope protein, TP1 and TP2, respectively, were tested for their antiviral activity. TP1 and TP2 inhibited TMUV infection in BHK-21 cells, and their 50% inhibitory concentrations (IC) were 14.19 mg/L and 7.64 mg/L, respectively. Viral inhibition assays in different cell lines of avian origin showed that the inhibitory effects of TP1 and TP2 are not cell type dependent. Moreover, TP2 also exhibited inhibitory activity against Japanese encephalitis virus (JEV) infection. The two peptides inhibited antibody-mediated TMUV infection of duck peripheral blood lymphocytes. Co-immunoprecipitation assays and indirect enzyme-linked immunosorbent assays (ELISAs) indicated that both peptides interact with the surface of the TMUV virion. RNase digestion assays confirmed the release of viral RNA following incubation with TP1, while incubation with TP1 or TP2 interfered with the binding between TMUV and cells. Taken together, these results show that TP1 and TP2 may be developed into antiviral treatments against TMUV infection.
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http://dx.doi.org/10.1016/j.vetmic.2020.108708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204726PMC
June 2020

Tembusu virus enters BHK-21 cells through a cholesterol-dependent and clathrin-mediated endocytosis pathway.

Microb Pathog 2020 Oct 12;147:104242. Epub 2020 May 12.

Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, Nanjing, China. Electronic address:

Tembusu virus (TMUV) is a newly emerging flavivirus and has caused significant economic loss to the poultry industry in China. To date, the entry of TMUV into host cells remains poorly understood. Here, the mechanism of TMUV entry into BHK-21 cells was investigated. The depletion of cellular cholesterol by methyl-β-cyclodextrin led to a significant decline in the titers and RNA levels of the infectious TMUV. This reduction was restored by supplementation of exogenous cholesterol. Membrane cholesterol depletion mainly blocked viral internalization but not attachment. However, viral infection was unaffected by genistein treatment or caveolin-1 silencing by small interfering RNA. In addition, clathrin-mediated endocytosis might be utilized in TMUV entry given that the viral infection was inhibited by knockdown of clathrin heavy chain and treatment of chlorpromazine (CPZ). Moreover, the number of internalized virus particles decreased under CPZ treatment. Dynasore inhibited TMUV entry suggesting a role for dynamin. Our results reveal that TMUV entry into BHK-21 cells is dependent on cholesterol, clathrin and dynamin but not caveolae.
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http://dx.doi.org/10.1016/j.micpath.2020.104242DOI Listing
October 2020

Elevated First-Trimester Neutrophil Count Is Closely Associated With the Development of Maternal Gestational Diabetes Mellitus and Adverse Pregnancy Outcomes.

Diabetes 2020 07 24;69(7):1401-1410. Epub 2020 Apr 24.

Department of Endocrinology, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China

Chronic low-grade inflammation plays a central role in the pathophysiology of gestational diabetes mellitus (GDM). To investigate the ability of different inflammatory blood cell parameters in predicting the development of GDM and pregnancy outcomes, 258 women with GDM and 1,154 women without were included in this retrospective study. First-trimester neutrophil count outperformed white blood cell count and the neutrophil-to-lymphocyte ratio in the predictability for GDM. Subjects were grouped based on tertiles of neutrophil count during their first-trimester pregnancy. The results showed that as the neutrophil count increased, there was a stepwise increase in GDM incidence as well as in glucose and glycosylated hemoglobin levels, HOMA for insulin resistance (HOMA-IR), macrosomia incidence, and newborn weight. Neutrophil count was positively associated with prepregnancy BMI, HOMA-IR, and newborn weight. Additionally, neutrophil count was an independent risk factor for the development of GDM, regardless of the history of GDM. Spline regression showed that there was a significant linear association between GDM incidence and the continuous neutrophil count when it was >5.0 × 10/L. This work suggested that the first-trimester neutrophil count is closely associated with the development of GDM and adverse pregnancy outcomes.
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http://dx.doi.org/10.2337/db19-0976DOI Listing
July 2020

Global gene expression analysis data of chicken dendritic cells infected with H9N2 avian influenza virus.

Data Brief 2020 Jun 16;30:105430. Epub 2020 Mar 16.

Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, and Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, Nanjing, Jiangsu, China.

This data article reports the global gene expression analysis data of chicken DCs infected with H9N2 avian influenza virus (AIV) compared with mock infection. The differentially expressed genes (DEGs), and the data of GO enrichment analysis and KEGG pathway analysis for DEGs were reported here. In addition, some of these DEGs associated with innate immune response and antigen presentation were also verified by qPCR. The replication of H9N2 AIV in DCs, and the viability kinetic of DCs during H9N2 AIV infection, and the primers for qPCR were also reported in this data article. The data presented here was used on the research article entitled "Transcriptomic profile of chicken bone marrow-derive dendritic cells in response to H9N2 avianinfluenza A virus".
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http://dx.doi.org/10.1016/j.dib.2020.105430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7152653PMC
June 2020

Targeting ferroptosis alleviates methionine-choline deficient (MCD)-diet induced NASH by suppressing liver lipotoxicity.

Liver Int 2020 06 20;40(6):1378-1394. Epub 2020 Mar 20.

Department of Endocrinology of the Fifth People's Hospital of Shanghai and the Molecular and Cell Biology Lab of the Institutes of Biomedical Sciences, Fudan University, Shanghai, China.

Background: NASH is one of the fastest growing liver diseases that leads to severe steatosis, inflammation and ultimately liver injury. However, the pathophysiological mechanisms of NASH remain unclear and pharmacological treatment against the disease is unavailable currently. Ferroptosis is a non-apoptotic form of cell death induced by iron-dependent lipid peroxidation. Since NASH progression is accompanied by massive lipid accumulation, which generates lipotoxic species, we investigated the role of ferroptosis in NASH progression.

Method: Mice were fed on MCD-diet to mimic NASH progression and gene expression in liver was analysed by RNA-seq. The occurrence of hepatic ferroptosis was measured by lipid ROS level, electron microscopy and in vivo PI staining. The beneficial effects of ferroptosis inhibitors on NASH was evaluated by liver pathology analysis. The mechanism of lipid ROS induced lipid droplets accumulation was investigated by in vitro cell culture.

Results: RNA-seq analysis suggested that elevated arachidonic acid metabolism promotes ferroptosis in MCD-diet fed mouse livers, which was further demonstrated by lipid ROS accumulation, morphological change of mitochondria and increased cell death. Iron accumulation was detected in the liver and the serum of MCD-fed mice. Scavenging of ferroptosis-linked lipid peroxides reduced lipid accumulation both in vivo and in vitro. Importantly, ferroptosis inhibitors alleviated MCD-diet induced inflammation, fibrogenesis and liver injury. Finally, lipid ROS promotes liver steatosis by boosting lipid droplets formation.

Conclusion: Our results demonstrate an important role of ferroptosis in the progression of MCD-diet induced NASH and suggest that ferroptosis may serve as a therapeutic target for NASH treatment.
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http://dx.doi.org/10.1111/liv.14428DOI Listing
June 2020

High Expression of Cancer-Derived Glycosylated Immunoglobulin G Predicts Poor Prognosis in Pancreatic Ductal Adenocarcinoma.

J Cancer 2020 3;11(8):2213-2221. Epub 2020 Feb 3.

Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.

: Cancer-derived immunoglobulin G (CIgG) has been detected in various cancers and plays important roles in carcinogenesis. The present study aimed to investigate its clinical significance in pancreatic ductal adenocarcinoma (PDAC). : Using tissue microarrays (TMAs) and immunohistochemistry, we assessed CIgG expression in 326 patients who underwent surgical resection for PDAC. The associations between CIgG expression and clinicopathological features and clinical outcomes were analyzed. Functional experiments were also performed to investigate the effect of CIgG on PDAC cells. : High CIgG expression was related to poor tumor differentiation and metastasis during follow-up and was associated with poor disease-free survival (DFS) and overall survival (OS). A multivariate Cox regression analysis identified high CIgG expression as an independent prognostic factor for DFS and OS. The incorporation of CIgG expression improved the accuracy of an established prognosis prediction model for 1-year OS and 2-year OS. studies showed that knocking down CIgG profoundly suppressed the proliferation, migration, and invasion capacity of PDAC cells. : CIgG contributes to the malignant behaviors of PDAC and offers a powerful prognostic predictor for these patients.
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http://dx.doi.org/10.7150/jca.39800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052941PMC
February 2020

IRON DEFICIENCY, A RISK FACTOR FOR THYROID AUTOIMMUNITY DURING SECOND TRIMESTER OF PREGNANCY IN CHINA.

Endocr Pract 2020 Jun 22;26(6):595-603. Epub 2020 Jan 22.

Previous studies have reported an association between iron deficiency (ID) and increased thyroid peroxidase antibody (TPO-Ab) during early pregnancy. The objective of this study was to explore the relationship between ID and thyroid dysfunction, as well as thyroid autoantibodies, during the second trimester of pregnancy. A total of 1,592 pregnant women (13 to 28 weeks gestation) were enrolled in this cross-sectional study. According to serum ferritin (SF) concentrations, they were divided into ID (SF <20 μg/L) or non-ID (SF ≥20 μg/L) groups. Logistic regression analysis was used to evaluate the association between ID and subclinical hypothyroidism (thyroid-stimulating hormone [TSH] >4.0 mIU/L and free thyroxine [FT4] within the reference range) and thyroid autoimmunity. The prevalence of ID was 23.43% (373/1,592). Compared with the non-ID group, the ID group had lower FT4 levels (13.94 pmol/L [8.91 to 29.82 pmol/L] versus 14.63 pmol/L [8.22 to 47.24 pmol/L]; <.001]) and higher TSH levels (1.85 mIU/L [0.01 to 7.84 mIU/L] versus 1.69 mIU/L [0.01 to 10.2 mIU/L]; <.05). Logistic regression analysis confirmed ID as a risk factor for increased thyroglobulin antibody (TG-Ab) (odds ratio 1.974; 95% confidence interval 1.065, 3.657; <.05), but not for subclinical hypothyroidism or increased TPO-Ab. ID is associated with increased TG-Ab during the second trimester of pregnancy. = body mass index; = coefficient of variation; = free thyroxine; = hemoglobin; = iron deficiency; = iron deficiency anemia; = serum ferritin; = triiodothyronine; = thyroxine; = thyroid autoimmunity; = thyroglobulin; = thyroglobulin antibody; = thyroid peroxidase; = thyroid peroxidase antibody; = thyroid-stimulating hormone.
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http://dx.doi.org/10.4158/EP-2019-0220DOI Listing
June 2020

Hepatic TET3 contributes to type-2 diabetes by inducing the HNF4α fetal isoform.

Nat Commun 2020 01 17;11(1):342. Epub 2020 Jan 17.

Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, 06510, USA.

Precise control of hepatic glucose production (HGP) is pivotal to maintain systemic glucose homeostasis. HNF4α functions to stimulate transcription of key gluconeogenic genes. HNF4α harbors two promoters (P2 and P1) thought to be primarily active in fetal and adult livers, respectively. Here we report that the fetal version of HNF4α is required for HGP in the adult liver. This isoform is acutely induced upon fasting and chronically increased in type-2 diabetes (T2D). P2 isoform induction occurs in response to glucagon-stimulated upregulation of TET3, not previously shown to be involved in HGP. TET3 is recruited to the P2 promoter by FOXA2, leading to promoter demethylation and increased transcription. While TET3 overexpression augments HGP, knockdown of either TET3 or the P2 isoform alone in the liver improves glucose homeostasis in dietary and genetic mouse models of T2D. These studies unmask an unanticipated, conserved regulatory mechanism in HGP and offer potential therapeutic targets for T2D.
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http://dx.doi.org/10.1038/s41467-019-14185-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969024PMC
January 2020

Transcriptomic profile of chicken bone marrow-derive dendritic cells in response to H9N2 avian influenza A virus.

Vet Immunol Immunopathol 2020 Feb 9;220:109992. Epub 2019 Dec 9.

Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, and Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, Nanjing, Jiangsu, 50 Zhongling Street, 210014, China. Electronic address:

Avian influenza subtype H9N2 infection is a mild but highly contagious disease that is associated with a decrease in the efficacy of vaccine interventions, and an increase in susceptibility to secondary infections in poultry. However, the immune evasion mechanism of H9N2 avian influenza viruses (AIVs) in chickens is poorly understood. Dendritic cells (DCs) are immune cells of major importance, involved in innate immune responses against viruses, but also in the setting of adaptive immune response due to their high ability to present viral antigen. Therefore, in the present study we used high-throughput RNA-sequencing technology at the transcriptome level to identify the differentially expressed genes (DEGs) between chicken DCs infected with H9N2 virus and mock-infected DCs. We identified 4151 upregulated DEGs and 2138 downregulated DEGs. Further enrichment analysis showed that the upregulated DEGs were enriched in the biological processes mainly involved in signal transduction, transmembrane transport, and innate immune/inflammatory responses. In contrast, the downregulated DEGs were associated with the biological processes mainly including metabolic process, and MHC class I antigen processing and presentation. In addition, 49 of these immune-related DEGs were validated by reverse transcription quantitative PCR (RT-qPCR). Collectively, these data suggest that H9N2 virus infection may enhance the signal transduction, and innate immune responses in chicken DCs, but impair their metabolic functions and antigen-presenting responses, which provide helpful insight into the pathogenesis of H9N2 AIVs in chickens and managing this infection in poultry farms.
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http://dx.doi.org/10.1016/j.vetimm.2019.109992DOI Listing
February 2020

Association between body mass index and effectiveness of continuous positive airway pressure in patients with obstructive sleep apnea: a retrospective study.

Sleep Breath 2020 Sep 18;24(3):1075-1081. Epub 2019 Nov 18.

Department of Intensive Care, Zhejiang Hospital, No. 12 Linyin Road, Hangzhou, Zhejiang, 310000, People's Republic of China.

Purpose: Ineffective use of continuous positive airway pressure (CPAP) therapy can result in inconvenience and additional costs in patients with obstructive sleep apnea (OSA). This study investigated the predictive value of body mass index (BMI) to assess the efficacy of CPAP in patients with OSA.

Methods: Data were extracted from a retrospective study performed in Silkeborg Hospital. The primary outcome was the improvement of Apnea-Hypopnea Index (AHI) after CPAP treatment. Association between BMI and improvement of AHI was assessed by multivariable linear regression. Interactions between BMI, baseline AHI severity (≥ 30 or < 30), and diabetes were also evaluated.

Results: Four hundred eighty-one patients were included in the study. After adjusting for confounders, high BMI (coefficient [coef], 0.80; 95% confidence interval [CI], 0.59-1.00; p < 0.001) and high AHI severity (AHI ≥ 30) (coef, 29.2; 95% CI, 26.7-31.7; p < 0.001) were associated with greater improvement of AHI after CPAP treatment, while diabetes was associated with less improvement of AHI (coef, - 4.91; 95% CI, - 9.40 to - 0.42; p = 0.032). Baseline AHI severity, diabetes, and BMI showed significant interactions (p < 0.001). On subgroup analysis, the association between BMI and improvement of AHI remained significant only in patients belonging to high AHI severity subgroup (coef, 1.18; 95% CI, 0.8-1.49; p < 0.001) and that without diabetes (coef, 1.42; 95% CI, 1.11-1.72; p < 0.001).

Conclusions: Patients with OSA having high BMI, without diabetes, are more likely to benefit from CPAP therapy. Future studies should explore the predictors of the efficacy of CPAP in more depth.
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http://dx.doi.org/10.1007/s11325-019-01960-xDOI Listing
September 2020

Berberine (BBR) Attenuated Palmitic Acid (PA)-Induced Lipotoxicity in Human HK-2 Cells by Promoting Peroxisome Proliferator-Activated Receptor α (PPAR-α).

Med Sci Monit 2019 Oct 14;25:7702-7708. Epub 2019 Oct 14.

Department of Endocrinology, Shanghai Fifth People's Hospital Affiliated to Fudan University, Shanghai, China (mainland).

BACKGROUND Berberine (BBR), a natural alkaloid isolated from Coptis chinensis, has frequently been reported as an antidiabetic reagent, partly due to its lipid-lowering activity. Evidence suggests that BBR ameliorates palmitate-induced lipid deposition and apoptosis in renal tubular epithelial cells (TECs), which tracks in tandem with the enhancement of peroxisome proliferator-activated receptor alpha (PPAR-alpha). The study aim was to investigate the roles of BBR in renal lipotoxicity in vitro, and investigate whether PPAR-alpha was the underlying mechanism. MATERIAL AND METHODS Human TECs (HK-2 cells) were injured with palmitic acid (PA), and then treated with BBR, BBR+PPAR-alpha inhibitor (GW6471), and PA+PPAR-alpha agonist (fenofibrate). Endoplasmic reticulum (ER) stress was assessed by measuring the expression of prospective evaluation of radial keratotomy (PERK), C/EBP-homologous protein (CHOP), and 78 kDa glucose-regulated protein (GRP78). Lipid metabolism was assessed by determining lipid anabolism-associated genes, including fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and lipoprotein lipase (LPL), as well as lipid catabolism-associated gene, including carnitine palmitoyl transferase 1 (CPT1). Inflammatory response of HK-2 cells was evaluated by measuring interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha. Cell apoptosis and protein levels of cleaved-caspase-3 were evaluated. RESULTS PA downregulated PPAR-alpha and induced server lipotoxicity in HK-2 cells by ER stress, increasing lipid deposition, and elevating inflammatory response of HK-2 cells accompanied with inducting cell apoptosis and cleaved-caspase-3, which were obviously reversed by additional treatment of BBR or PPAR-alpha agonist. However, the protective effect of BBR in PA-induced lipotoxicity in HK-2 cells was significantly ameliorated by PPAR-alpha inhibitor. CONCLUSIONS BBR attenuated PA-induced lipotoxicity via the PPAR-alpha pathway.
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http://dx.doi.org/10.12659/MSM.916686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6812469PMC
October 2019

GESTATIONAL WEIGHT GAIN AS AN INDEPENDENT RISK FACTOR FOR MACROSOMIA IN WOMEN WITH INTERMEDIATE STATE GESTATIONAL BLOOD GLUCOSE.

Endocr Pract 2019 Nov 15;25(11):1158-1165. Epub 2019 Aug 15.

Macrosomia is closely associated with gestational diabetes mellitus (GDM) but its relationship with maternal intermediate state gestational blood glucose (ISGBG; normal fasting blood glucose and 7.8 mmol/L <1 hour blood glucose [BG] <10 mmol/L or 6.7 mmol/L <2 hour BG <8.5 mmol/L) is unclear. Here, we analyzed the clinical characteristics and pregnancy outcomes and explored risk factors for macrosomia in women with ISGBG. A total of 847 women with normal glucose tolerance gestation, 330 with ISGBG, and 99 with GDM were included. Maternal and fetal clinical data were collected and 3-point BG following oral glucose tolerance test, fasting insulin, glycated hemoglobin, and blood lipids profile were measured. The incidence rate of macrosomia among the neonates of women with ISGBG was as high as 10.9%. In the ISGBG group, prepregnancy body mass index (BMI), gestational weight gain (GWG) and the proportion of women with excessive GWG (eGWG) were significantly higher in women with macrosomia compared with those who delivered a normal weight neonate. In women with ISGBG, neonate weight was positively correlated with maternal prepregnancy weight ( = 0.183, <.01), prepregnancy BMI ( = 0.135, <.01), and GWG ( = 0.255, <.01), and negatively correlated with high-density lipoprotein cholesterol ( = -0.172, <.01). Nonetheless, only eGWG was an independent risk factor (odds ratio = 3.18, 95% confidence interval = 1.26 to 7.88, <.05) for macrosomia. The risk of macrosomia in pregnant women with prepregnancy BMI <25 kg/m or BMI ≥25 kg/m and eGWG was 3.39 and 3.27 times, respectively. The incidence rate of macrosomia is increased in women with ISGBG and eGWG is the strongest independent risk factor. In order to reduce the risk for macrosomia, timely lifestyle intervention to promote appropriate weight gain during pregnancy deserves evaluation. = area under the curve; = blood glucose; = 1 hour blood glucose after OGTT; = 2 hour blood glucose after OGTT; = body mass index; = confidence interval; = excessive gestational weight gain; = fasting blood glucose; = fasting insulin; = gestational diabetes mellitus; = glycated hemoglobin; = high-density lipoprotein cholesterol; = homeostasis model assessment of insulin resistance index; = intermediate state gestation blood glucose; = low-density lipoprotein cholesterol; = natural logarithm; = mature low birth weight; = normal glucose tolerance gestation; = oral glucose tolerance test; = odds ratio; = standard deviation.
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http://dx.doi.org/10.4158/EP-2018-0558DOI Listing
November 2019

Cancer IgG, a potential prognostic marker, promotes colorectal cancer progression.

Chin J Cancer Res 2019 Jun;31(3):499-510

Department of Gastroenterological Surgery, Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People's Hospital, Beijing 100044, China.

Objective: Currently, no satisfactory targets for colorectal cancer or markers for immunotherapy and diagnosis and prognosis are available. Immunoglobulin G (IgG) is widely expressed in many cancers, and it promotes cancer progression. This study explored the role of cancer-derived IgG (CIgG) in colorectal cancer.

Methods: First, using a monoclonal antibody to CIgG, we examined the expression levels of CIgG in colorectal cancer cell lines by western blot and immunofluorescence analyses and in tissue specimens by immunohistochemistry. Second, the variable region gene was amplified by nested polymerase chain reaction (PCR), and PCR products were sequenced and analyzed. Third, we investigated the effect of CIgG on colorectal cancer cells by cell proliferation, wound healing, migration and invasion assays, and colony formation assay. Fourth, we performed tumorigenicity experiments to explore the effect of CIgG on tumorigenicity. Finally, we used RNA-seq analysis and co-immunoprecipitation experiments to further clarify possible mechanisms of CIgG.

Results: We found that CIgG is widely expressed in colorectal cancer cells, and the overexpression of CIgG indicates significantly poor colorectal cancer prognosis. Furthermore, CIgG knockdown significantly inhibits the proliferation, migration and invasion ability of cells, and tumor growth . RNA-seq analysis indicated that CIgG knockdown results primarily in changes in expression of apical junction and epithelial-mesenchymal transition-related genes. CIgG may be involved in colorectal cancer invasion and metastasis through interacting with E-cadherin.

Conclusions: CIgG is a potential human oncogene in colorectal cancer and that it has potential for application as a novel target in targeted therapy and a marker for prognostic evaluation.
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http://dx.doi.org/10.21147/j.issn.1000-9604.2019.03.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613500PMC
June 2019

The ubiquitin-proteasome system is necessary for the replication of duck Tembusu virus.

Microb Pathog 2019 Jul 1;132:362-368. Epub 2019 May 1.

Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, National Center for Engineering Research of Veterinary Bio-products, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, PR China. Electronic address:

Duck Tembusu virus (DTMUV) is a newly emerging pathogenic flavivirus that has caused massive economic losses to the duck industry in China. The cellular factors required for DTMUV replication have been poorly studied. The ubiquitin-proteasome system (UPS), the major intracellular proteolytic pathway, mediates diverse cellular processes, including endocytosis and signal transduction, which may be involved in the entry of virus. In the present study, we explored the interplay between DTMUV replication and the UPS in BHK-21 cells and found that treatment with proteasome inhibitor (MG132 and lactacystin) significantly decreased the DTMUV progency at the early infection stage. We further revealed that inhibition of the UPS mainly occurs on the level of viral protein expression and RNA transcription. In addition, using specific siRNAs targeting ubiquitin reduces the production of viral progeny. In the presence of MG132 the staining for the envelope protein of DTMUV was dramatically reduced in comparison with the untreated control cells. Overall, our observations reveal an important role of the UPS in multiple steps of the DTMUV infection cycle and identify the UPS as a potential drug target to modulate the impact of DTMUV infection.
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http://dx.doi.org/10.1016/j.micpath.2019.04.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7126904PMC
July 2019

Platelet-to-lymphocyte ratio as a prognostic predictor of mortality for sepsis: interaction effect with disease severity-a retrospective study.

BMJ Open 2019 01 25;9(1):e022896. Epub 2019 Jan 25.

Department of Intensive Care Unit, Dongyang People's Hospital, Jinhua, P.R. China.

Objective: The role of platelet-to-lymphocyte ratio (PLR) as an indicator of inflammation has been the focus of research recently. We aimed to investigate the value of PLR for sepsis.

Design: A retrospective cohort study.

Setting And Participants: Data were extracted from the Multiparameter Intelligent Monitoring in Intensive Care III database. Data on 5537 sepsis patients were analysed.

Methods: Logistic regression was used to explore the association between PLR and hospital mortality. Subgroup analyses were performed based on vasopressor use, acute kidney injury (AKI) and a Sequential Organ Failure Assessment (SOFA) score >10.

Results: In the logistic model with linear spline function, a PLR >200 was significantly (OR 1.0002; 95% CI 1.0001 to 1.0004) associated with mortality; the association was for PLRs ≤200 (OR 0.997; 95% CI 1.19 to 1.67). In the logistic model using the PLR as a design variable, only high PLRs were significantly associated with mortality (OR 1.29; 95% CI 1.09 to 1.53); the association with low PLRs was (OR 1.15; 95% CI 0.96 to 1.38). In the subgroups with vasopressor use, AKI and a SOFA score >10, the association between high PLR and mortality was ; this remained significant in the subgroups without vasopressor use (OR 1.39; 95% CI 1.08 to 1.77) and AKI (OR 1.54; 95% CI 1.20 to 1.99) and with a SOFA score ≤10 (OR 1.51; 95% CI 1.17 to 1.94).

Conclusions: High PLRs at admission were associated with an increased risk of mortality. In patients with vasopressor use, AKI or a SOFA score >10, this association was
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http://dx.doi.org/10.1136/bmjopen-2018-022896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352809PMC
January 2019

The unfolded protein response induced by Tembusu virus infection.

BMC Vet Res 2019 Jan 22;15(1):34. Epub 2019 Jan 22.

Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Jiangsu Province, 210014, People's Republic of China.

Background: Tembusu virus (TMUV), classified in the genus Flavivirus, causes reduced egg production and neurological problems in poultry. Flavivirus replication depends on the host endoplasmic reticulum (ER) and induces ER stress that leads to activation of the cellular unfolded protein response (UPR), an important signalling pathway that regulates many biological functions involved in viral pathogenesis and innate immunity. However, the mechanism of TMUV-induced UPR activation remains unclear.

Results: In this study, we systematically investigated the three UPR pathways in TMUV-infected BHK-21 cells. Our results showed that expression of glucose-related protein 78 (GRP78) and GRP94 was upregulated during the course of TMUV infection. We then demonstrated that TMUV activated the PERK pathway in the early stage of infection, resulting in upregulation of ATF4, GADD34 and CHOP, with CHOP induction leading to caspase-3 activation. We also found the IRE1 pathway to be activated, leading to splicing of X box binding protein 1 (XBP1) mRNA and enhanced expression of p58. Finally, we observed increased expression of ATF6 and activity of ER stress-response elements, suggesting stimulation of the ATF6 pathway. In addition, ATF6 pathway activation correlated with the induction of downstream chaperones calnexin, calreticulin, ERp57 and PDI. UPR activity was also observed by the marked elevation in GRP78 and sXBP1 levels in TMUV-infected DF-1 cells.

Conclusions: This is the first report that TMUV infection-induced ER stress activates three branches of the UPR, and these results lay the foundation for elucidating the pathogenesis of TMUV and understanding the inherent mechanism of TMUV infection as well as the host response.
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http://dx.doi.org/10.1186/s12917-019-1781-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343269PMC
January 2019

Association of High Prolactin Level on Postoperative Day 1 and Tumor Invasion with Female Gonadal Dysfunction After Trans-Sphenoidal Surgery of Pituitary Adenomas.

Med Sci Monit 2018 Dec 20;24:9265-9271. Epub 2018 Dec 20.

Department of Endocrinology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China (mainland).

BACKGROUND The aim of this study was to evaluate the risk factors of gonadal dysfunction among Chinese women of reproductive age with pituitary adenomas (PAs) after trans-sphenoidal surgery. MATERIAL AND METHODS We retrospectively evaluated 317 women (16-44 years old) who underwent gonadal function and hormone testing before and after trans-sphenoidal surgery for PAs during 2003-2012. Gonadal function was assessed on the basis of menstrual status. RESULTS Three women were excluded because of pre-existing gynecological diseases. Before trans-sphenoidal surgery, 34 (10.7%) women were eugonadal and 283 (89.3%) women had gonadal dysfunction. After trans-sphenoidal surgery, 130/189 (68.7%) women with follow-up menstruation data were eugonadal, and 59/189 (31.2%) women exhibited gonadal dysfunction. In addition, 67.4% women of reproductive age with PAs and gonadal dysfunction were restored by trans-sphenoidal surgery (P<0.01). Postoperative gonadal dysfunction was independently associated with high prolactin level at day 1 after trans-sphenoidal surgery (odds ratio (OR)=1.024; 95% confidence interval (CI)=1.005-1.043; P=0.012) and tumor invasion (OR=5.752; 95%CI=1.618-20.447; P<0.01). Based on the receiver operating characteristic (ROC) curve, prediction of gonadal dysfunction in women of reproductive age after trans-sphenoidal surgery for PAs using prolactin >46.82 µg/L on postoperative day 1 had sensitivity of 88%, specificity of 95%, positive predictive value of 98%, and negative predictive value of 76%, and an area under the ROC curve of 0.701. CONCLUSIONS Gonadal dysfunction is very common in Chinese women of reproductive age with PAs and can be effectively restored by trans-sphenoidal surgery. Prolactin >46.82 µg/L at 1 day after trans-sphenoidal surgery and tumor invasion can predict postoperative gonadal dysfunction in these patients.
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http://dx.doi.org/10.12659/MSM.910348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320648PMC
December 2018

Positive fluid balance is associated with increased in-hospital mortality in patients with intracerebral hemorrhage.

Brain Inj 2019 13;33(2):212-217. Epub 2018 Nov 13.

Department of Intensive Care Unit, Zhejiang Provincial Hospital of TCM, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, P.R. China.

: This study aimed to investigate the association between fluid balance (FB) and in-hospital mortality in patients with intracerebral hemorrhage (ICH).: Data were extracted from the online database Multi-parameter Intelligent Monitoring in Intensive Care III. Patients were divided into two groups according to the FB status at 48 hours after intensive care unit (ICU) admission: negative and positive 48-hour FB groups. The primary outcome was in-hospital mortality.: Data of 1407 patients were analyzed. Linear spline function in logistic models showed significant association between the volume of positive FB and in-hospital mortality (odds ratio (OR) 1.006; 95% CI: 1.002-1.010), while the association between the volume of negative FB and in-hospital mortality was non-significant. For interpretation, FB was further divided into four quartiles. Referred to Q1, the OR of in-hospital mortality stepwise increased from Q2 (OR, 1.11; 95% CI: 0.72-1.68) to Q4 (OR, 1.68; 95% CI: 1.13-2.48). A similar association was also found between FB and Glasgow coma scale at ICU discharge.: In patients with ICH, increased volume of positive FB was associated with higher in-hospital mortality while the volume of negative FB was not. Whether maintaining a zero FB status is a beneficial strategy needs further investigation.
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http://dx.doi.org/10.1080/02699052.2018.1539870DOI Listing
October 2020

Ameliorative effect of berberine coated bio-active nanoparticles in acetaminophen induced hepato-renal damage in diabetic rats.

J Photochem Photobiol B 2018 Dec 17;189:250-257. Epub 2018 Oct 17.

Department of Endocrinology, Shanghai Fifth People's Hospital Affiliated to Fudan University, Shanghai 200240, PR China.. Electronic address:

The current investigation was performed for the detailed analysis of protective effect of biofabricate berberine coated nano‑silver ameliorate (BBR-AgNPs) on acetaminophen (APAP) induced hepato-renal damages in diabetic rats by blood biochemistry, tissue biochemistry, histopathological and immunohistochemical analysis. The spherical shaped BBR-AgNPs were synthesized by the Biofabrication technique and its physico-chemical characterizations done by different spectroscopic (UV-vis spectrophotometer, XRD spectroscopy, FTIR spectroscopy EDAX & DLS analyses) and microscopic (FE-SEM) techniques. The diabetic developed rats were administrated with APAP (2.0 g/5 mL/kg) and scrutinize its hepato-renal injuries. The synthesized BBR-AgNPs (75 mg/kg p.o) was administrated orally to the APAP-induced diabetic rats. The result of biochemical markers and lipid peroxidation were significantly (P ˂ 0.05) increased in APAP-induced diabetic rats but decreased the level of antioxidants (P ˂ 0.05), which results obtained in liver and kidney compared to the control group. Immunohistochemical studies result showed that the APAP-induced diabetic rats expressed a high immunoreactivity of nuclear transcription factor (NF-kB). Whereas, the acetaminophen-induced diabetic rats were treated with BBR-AgNPs renovated the changes in the above parameters analyzed. The results of the study clearly indicated that the BBR-AgNPs possess the antioxidant properties as well as anti-diabetic effects, furthermore, the acetaminophen-induced liver and kidney damage was probably inhibited by the inhibition of proinflammatory factor & NF-kB factors.
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http://dx.doi.org/10.1016/j.jphotobiol.2018.10.015DOI Listing
December 2018

Identification and immunogenic evaluation of T cell epitopes based on tembusu virus envelope protein in ducks.

Virus Res 2018 09 18;257:74-81. Epub 2018 Sep 18.

Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Jiangsu Province, PR China; Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, Nanjing, Jiangsu Province, PR China. Electronic address:

Newly emerging tembusu virus (TMUV) is a severe threat to poultry industry and causes huge economic losses. Humoral and cell-mediated immunity are both play vital roles in TMUV infection. Up to now, there has been no report on identification of T cell epitopes of the TMUV. In this work, we identified T cell epitopes within TMUV envelope (E) protein using synthesized peptides predicted in silico. A total of ten peptides could stimulate TMUV-specific T cells in murine ELISPOT and duck lymphocyte proliferation assay. Subsequently, DNA vaccine containing these T cell epitopes was constructed (pVAX-T) and the expression of multiepitope protein was confirmed by transfection of BHK-21 cells in vitro. Ducks were administrated intramusclarly to evaluated the immunologic effect of pVAX-T. In ducks immunized with pVAX-T, antibody against TMUV was undetectable, but the expression level of cytokines (IL-2, IL-6, IFN-γ) was upregulated both in peripheral blood lymphocytes and spleen. Furthermore, TMUV challenge revealed that cell-mediated immune response sitmulated by pVAX-T contributed to protection against TMUV infection. The identification of these T cell epitopes will contribute to designing epitope vaccine for preventing infection of TMUV and possibly provide the basis for further studies on cell-mediate immune response activated by TMUV.
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http://dx.doi.org/10.1016/j.virusres.2018.09.008DOI Listing
September 2018

Screening and identification of B-cell epitopes within envelope protein of tembusu virus.

Virol J 2018 09 17;15(1):142. Epub 2018 Sep 17.

Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, 50 Zhongling Street, Nanjing City, Jiangsu Province, 210014, People's Republic of China.

Background: Tembusu virus is a newly emerging flavivirus that caused egg-drop syndrome in ducks in China. TMUV envelope protein is a major structural protein locates at the surface of tembusu virus particle. During tembusu virus infection, envelope protein plays a pivotal role in induction of neutralizing antibody. However, B cell epitopes within envelope protein have not been well studied.

Method: A series of 13 peptides derived from E protein of tembusu virus were synthesized and screened by Dot blot with tembusu virus-positive duck serum. Potential B-cell epitopes were respectively fused with GST tag and expressed in E. coli. The immunogenicity and protective efficiency of epitopes were assessed in ducks.

Results: Dot blot assay identified the peptides P21 (amino acids 301-329), P23 (amino acids 369-387), P27 (amino acids 464-471) and P28 (amino acids 482-496) as potential B-cell epitopes within the envelope protein of tembusu virus. Immunization of prokaryotically expressed epitopes elicited specific antibodies in ducks and the specific antibody elicited by P21, P27 and P28 could neutralized tembusu virus. In addition, protective test suggested that P21 and P27 could completely protect immunized ducks from TMUV challenge.

Conclusion: Four potential B cell epiotpes within tembusu virus envelope protein were identified and analyzed in vitro and in vivo. It was demonstrated that two of them (P21 and P27) could elicit neutralizing antibodies in ducks and offer complete protection against tembusu virus challenge. This findings will contribute to the development of epitope vaccine for tembusu virus prevention.
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http://dx.doi.org/10.1186/s12985-018-1052-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6142368PMC
September 2018

The molecular characterization and protective efficacy of microneme 3 of Eimeria mitis in chickens.

Vet Parasitol 2018 Jul 25;258:114-123. Epub 2018 Jun 25.

MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China. Electronic address:

E. mitis is ubiquitous in clinical coccidiosis caused by mixed infection of Eimeria species and the infection by E. mitis usually significantly impairs productivity of the infected chickens. To date, however, few protective antigens from E. mitis have been reported. In this study, the molecular characterization and protective efficacy of microneme 3 of Eimeria mitis (EmiMIC3) were analyzed. EmiMIC3 gene was cloned from sporozoites of E. mitis and its MARs (microneme adhesive repeats domain) were predicted. Recombinant EmiMIC3 (rEmiMIC3) was expressed in E. coli and purified and then was analyzed by western blot with anti-E. mitis chicken serum. Meanwhile, native EmiMIC3 from sporozoites was analyzed by anti-rEmiMIC3 rat serum. The expressions of EmiMIC3 in E. mitis sporozoites and merozoites were analyzed by immunofluorescence assay. The rEmiMIC3-induced changes of T lymphocytes subpopulation, serum cytokines and IgY levels and the protective efficacy of rEmiMIC3 were determined in animal experiments. The results showed that the deduced open reading frame (ORF) of EmiMIC3 was composed of 1145 amino acids, possessing 9 MARs. EmiMIC3 gene was submitted to GenBank (accession number: MG888670). EmiMIC3 could express in sporozoites and merozoites respectively and located at the apex of E. mitis sporozoite. Western blot assay revealed that the rEmiMIC3 could be recognized by serum of chicken infected by E. mitis and the native EmiMIC3 from sporozoites could also be recognized by rat serum against rEmiMIC3. Following vaccination with rEmiMIC3, higher levels of IL-10, IFN-γ, TGF-βand IL-17, higher proportions of CD4+/CD3+ and CD8+/CD3 + T lymphocytes and higher level of IgY antibody were induced compared to the controls. Vaccination with rEmiMIC3 prominently increased the weight gains and decreased oocyst output of the vaccinated chickens after challenge infection. Our result not only enriches protective candidate antigen of E. mitis, but also provides available protective antigen of E. mitis for the development of multivalent vaccines against infection caused by mixture of Eimeria species in clinical coccidiosis.
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http://dx.doi.org/10.1016/j.vetpar.2018.06.020DOI Listing
July 2018

Time-related association between fluid balance and mortality in sepsis patients: interaction between fluid balance and haemodynamics.

Sci Rep 2018 Jul 10;8(1):10390. Epub 2018 Jul 10.

Department of Intensive Care Unit, Zhejiang Hospital, 12# Lingyin Road, Hangzhou, Zhejiang, 322100, P.R. China.

This study aimed to investigate the time-related association between cumulative fluid balance (FB) and mortality. Data were extracted from the Medical Information Mart for Intensive Care (MIMIC) III. FB data on 8584 patients at the first (FB-fir24hr) and second (FB-sec24hr) 24 hours after intensive care unit admission were analysed. Compared to the combination of FB-fir24hr ≤ 0 and FB-sec24 hr ≤ 0, the combination of FB-fir24hr > 0 and FB-sec24hr ≤ 0 had significantly higher FB, with an insignificant odds ratio (OR) for mortality. However, the mortality ORs of two other combinations (FB-fir24hr ≤ 0 and FB-sec24hr > 0; FB-fir24hr > 0 and FB-sec24hr > 0) were significantly high. Furthermore, multivariable logistic analysis showed a significant stepwise increase ORs for mortality with increasing FB-sec24hr quartiles, with no significant increase in FB-fir24hr quartiles aside from quartile 4. In patients with negative FB, a stepwise decrease in mortality ORs with increasing FB-sec24hr quartiles was found with no significant difference in FB-fir24hr quartiles. In conclusion, the positive FB during the second but not the first 24 hours was associated with increased mortality in sepsis. Achieving more negative FB was associated with decreased mortality only in the second 24 hours.
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http://dx.doi.org/10.1038/s41598-018-28781-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039532PMC
July 2018

Identification of determinants that mediate binding between Tembusu virus and the cellular receptor heat shock protein A9.

J Vet Sci 2018 Jul;19(4):528-535

Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, Nanjing 210014, China.

Heat shock protein A9 (HSPA9), a member of the heat shock protein family, is a putative receptor for Tembusu virus (TMUV). By using Western blot and co-immunoprecipitation assays, E protein domains I and II were identified as the functional domains that facilitate HSPA9 binding. Twenty-five overlapping peptides covering domain I and domain II sequences were synthesized and analyzed by using an HSPA9 binding assay. Two peptides showed the capability of binding to HSPA9. Dot blot assay of truncated peptides indicated that amino acid residues 19 to 22 and 245 to 252 of E protein constitute the minimal motifs required for TMUV binding to HSPA9. Importantly, peptides harboring those two minimal motifs could effectively inhibit TMUV infection. Our results provide insight into TMUV-receptor interaction, thereby creating opportunities for elucidating the mechanism of TMUV entry.
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http://dx.doi.org/10.4142/jvs.2018.19.4.528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070589PMC
July 2018