Publications by authors named "Xinyu Gu"

31 Publications

Uncovering the Association Between mC Regulator-Mediated Methylation Modification Patterns and Tumour Microenvironment Infiltration Characteristics in Hepatocellular Carcinoma.

Front Cell Dev Biol 2021 13;9:727935. Epub 2021 Sep 13.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

5-Methylcytosine (mC) plays essential roles in hepatocellular carcinoma (HCC), but the association between mC regulation and immune cell infiltration in HCC has not yet been clarified. In this study, we analysed 371 patients with HCC from The Cancer Genome Atlas (TCGA) database, and the expression of 13 mC regulators was investigated. Additionally, gene set variation analysis (GSVA), unsupervised clustering analysis, single-sample gene set enrichment analysis (ssGSEA), correlation analysis, and immunohistochemical (IHC) staining were performed. Among the 371 patients, 41 had mutations in mC regulators, the frequency of which was 11.26%. Compared with normal hepatic tissues, the expression of mC regulators with copy number variations (CNVs) expansion was significantly higher than that in HCC tissues. Then, we identified three mC modification patterns that had obvious tumour microenvironment (TME) cell infiltration characteristics. The prognostic analysis of the three major mC modification subtypes showed that Cluster-2 had a clear survival advantage over the others. In addition, we found that DNMT1 was highly expressed in tumour tissues compared with normal tissues in a tissue microarray (TMA) and that it was positively correlated with many TME-infiltrating immune cells. High expression of the mC regulator DNMT1 was related to a poor prognosis in patients with HCC. Furthermore, we developed three distinct Immu-clusters. Importantly, mRNAs related to the transcription of growth factor β (TGF-β)/EMT pathway were significantly up-regulated in Immu-cluster 2, indicating that this cluster is considered to be the immune rejection phenotype. Immu-cluster 3 showed elevated expression of mRNAs related to immune checkpoint genes. Our work revealed the association between mC modification and immune regulators in the TME. These findings also suggest that DNMT1 has great potential as a prognostic biomarker and therapeutic target for HCC.
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http://dx.doi.org/10.3389/fcell.2021.727935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475949PMC
September 2021

Molybdenum oxide-iron, cobalt, copper alloy hybrid as efficient bifunctional catalyst for alkali water electrolysis.

J Colloid Interface Sci 2021 Aug 28;606(Pt 2):1662-1672. Epub 2021 Aug 28.

School of Chemistry and Chemical Engineering, Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Normal University, Henan Xinxiang 453007, PR China. Electronic address:

Efficient and durable non-precious catalyst for both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is pivotal for practical water electrolysis toward clean hydrogen fuel. Herein, a molybdenum oxide-FeCoCu alloy hybrid (MoO-FeCoCu) catalyst was designed by polyoxometallate (POM) molecular cluster mediated solvothermal alcoholysis and ammonolysis of metal salts followed by pyrolytic reduction treatment. The HER efficiency is substantially enhanced by the ternary alloy component, which is more close to the benchmark Pt/C catalyst, and the HER catalytic stability is also superior to Pt/C catalyst. Moreover, the MoO-FeCoCu demonstrates high catalytic efficiency and rather good durability for OER. Benefitted by the bifunctional catalytic behaviors for HER and OER, the symmetric water electrolyzer based on the MoO-FeCoCu electrode requires a low driving voltage of 1.69 V to deliver a response current density of 10 mA cm, which is comparable to that based on the benchmark Pt/C HER cathode and RuO OER anode. The current work offers a feasible way to design efficient bifunctional catalyst for water electrolysis via POM mediated co-assembly and calcination treatment.
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http://dx.doi.org/10.1016/j.jcis.2021.08.174DOI Listing
August 2021

Immune classifier-based signatures provide good prognostic stratification and predict the clinical benefits of immune-based therapies for hepatocellular carcinoma.

Cancer Cell Int 2021 Sep 6;21(1):471. Epub 2021 Sep 6.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 Qingchun Road, Shangcheng District, Hangzhou, 310003, Zhejiang, China.

Background: Hepatocellular carcinoma (HCC) is an aggressive cancer with a high rate of death globally. The use of bioinformatics may help to identify immune cell-related genes both as targets for potential immunotherapies and for their value associated with predicting therapy responses.

Methods: In this study, mRNA expression profiles of HCC samples from The Cancer Genome Atlas (TCGA) database were subjected to gene enrichment, cell type abundance, immune cell infiltration, and pathway enrichment analyses to determine immune cell gene features, cell type abundance, and functional annotation characteristics. We also evaluated their prognostic values using Cox regression and Kaplan-Meier analyses and assessed potential responses to chemotherapy. Four subgroups (Groups 1-4) were identified. Group 4 was associated with advanced clinical characteristics, high immune cell enrichment scores, and the poorest outcomes.

Results: Differentially expressed genes (DEGs) in the HCC samples were enriched in the following pathways: antigen binding, cell surface receptor signal transduction of the immune response, and cell surface activated receptor signal transduction of the immune response. Highly expressed genes in Group 4 were enriched in elements of the WNT signalling pathway. We identified five immune-related genes (SEMA3A, TNFRSF11B, GUCA2A, SAA1, and CALCR) that were significantly related to HCC prognosis. A prognostic model based on these five genes exhibited good predictive value, with 1-year and 5-year area under the curve (AUC) values of  >  0.66. Group 4 was also potentially more sensitive to EHT 1864, FH535, and lapatinib chemotherapies than the other groups.

Conclusions: We identified and validated four HCC subgroups based on immune system-related genes and identified five genes that may be used for an immune-based prognostic model for HCC treatment.
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http://dx.doi.org/10.1186/s12935-021-02183-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422634PMC
September 2021

Immune signature-based hepatocellular carcinoma subtypes may provide novel insights into therapy and prognosis predictions.

Cancer Cell Int 2021 Jun 30;21(1):330. Epub 2021 Jun 30.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China.

Background: Hepatocellular carcinoma (HCC) has a poor prognosis and has become the sixth most common malignancy worldwide due to its high incidence. Advanced approaches to therapy, including immunotherapeutic strategies, have played crucial roles in decreasing recurrence rates and improving clinical outcomes. The HCC microenvironment is important for both tumour carcinogenesis and immunogenicity, but a classification system based on immune signatures has not yet been comprehensively described.

Methods: HCC datasets from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and the International Cancer Genome Consortium (ICGC) were used in this study. Gene set enrichment analysis (GSEA) and the ConsensusClusterPlus algorithm were used for clustering assessments. We scored immune cell infiltration and used linear discriminant analysis (LDA) to improve HCC classification accuracy. Pearson's correlation analyses were performed to assess relationships between immune signature indices and immunotherapies. In addition, weighted gene co-expression network analysis (WGCNA) was applied to identify candidate modules closely associated with immune signature indices.

Results: Based on 152 immune signatures from HCC samples, we identified four distinct immune subtypes (IS1, IS2, IS3, and IS4). Subtypes IS1 and IS4 had more favourable prognoses than subtypes IS2 and IS3. These four subtypes also had different immune system characteristics. The IS1 subtype had the highest scores for IFNγ, cytolysis, angiogenesis, and immune cell infiltration among all subtypes. We also identified 11 potential genes, namely, TSPAN15, TSPO, METTL9, CD276, TP53I11, SPINT1, TSPO, TRABD2B, WARS2, C9ORF116, and LBH, that may represent potential immunological biomarkers for HCC. Furthermore, real-time PCR revealed that SPINT1, CD276, TSPO, TSPAN15, METTL9, and WARS2 expression was increased in HCC cells.

Conclusions: The present gene-based immune signature classification and indexing may provide novel perspectives for both HCC immunotherapy management and prognosis prediction.
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http://dx.doi.org/10.1186/s12935-021-02033-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243542PMC
June 2021

Short-term effect of low-dose rituximab on myasthenia gravis with muscle-specific tyrosine kinase antibody.

Muscle Nerve 2021 06 6;63(6):824-830. Epub 2021 Apr 6.

Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.

Introduction/aims: The study aims to investigate the short-term efficacy of low-dose rituximab and its effect on immunological biomarker levels in myasthenia gravis (MG) patients with antibodies against muscle-specific tyrosine kinase (MuSK-MG).

Methods: Twelve MuSK-MG patients were enrolled in this prospective, open-label, self-controlled pilot study. Clinical severity was evaluated at baseline and 6 mo after a single rituximab treatment (600 mg). B lymphocyte subtypes, MuSK antibody titers, together with levels of immunoglobulins, serum B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), soluble CD40L, and four exosomal microRNAs were evaluated. A correlation matrix to reveal pairwise relationships among above variables was also generated.

Results: The single rituximab treatment significantly lowered the clinical severity scores and reduced daily dosage of prednisone (P = .032) at 6 mo. MuSK antibody titers decreased (P = .035) without significant changes in immunoglobulin levels. Serum BAFF level increased (P = .010), which negatively correlated with the percentages of B cells in lymphocytes as well as clinical severity. Additionally, serum exosomal miR-151a-3p showed a reduction of 28.1% (P = .031).

Discussion: We confirmed the clinical efficacy of low-dose rituximab in MuSK-MG, accompanied by a decrease in MuSK antibody titers and an increase in serum BAFF. Serum BAFF levels negatively correlated with B-cell counts as well as clinical severity.
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http://dx.doi.org/10.1002/mus.27233DOI Listing
June 2021

Improving the lipid extraction yield from Chlorella based on the controllable electroporation of cell membrane by pulsed electric field.

Bioresour Technol 2021 Jun 6;330:124933. Epub 2021 Mar 6.

Laboratory of Advanced Technology of Power & Electrical Engineering, Tsinghua Shenzhen International Graduate School(SIGS), Tsinghua University, Shenzhen, Guangdong, 518055, China.

In order to solve the increasingly serious problems of energy and environment, microalgae are used as a raw material for extracting lipids to produce biodiesel. Prior to the extraction of lipids, microalgae were treated with high-voltage pulsed electric field (PEF) to break the cell membrane. It was found that the lipid extraction yield depends on the electric field strength (E) and the specific energy input (Wsp), and has a certain relationship with the cell disintegration rate of Chlorella. The perforation degree of the Chlorella's cell membrane by PEF treatment is controllable, moderate perforation can be ensured by controlling the power parameters. PEF treatment significantly improved the extraction yield of lipids. Compared with the test samples without PEF treatment, PEF treatment increased the lipid extraction yields by up to 166.67%. However, an excessively high voltage will cause the quality of the extracted biodiesel to decrease.
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http://dx.doi.org/10.1016/j.biortech.2021.124933DOI Listing
June 2021

Transcription factor E2F4 is an indicator of poor prognosis and is related to immune infiltration in hepatocellular carcinoma.

J Cancer 2021 21;12(6):1792-1803. Epub 2021 Jan 21.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.

Recent studies have shown that the transcription factor E2F4 is involved in the progression of various tumors, but its expression and influence on immune cell infiltration and biological functions are largely unknown in hepatocellular carcinoma (HCC). The Cancer Genome Atlas (TCGA) database, the Tumor Immune Estimation Resource (TIMER) and related online tools as well as a tissue microarray (TMA) were used for analyses in our study. E2F4 expression was elevated in HCC tumor tissue compared with adjacent normal tissue at both the mRNA and protein levels. Overexpression of E2F4 was markedly related to a poor prognosis in HCC patients. In addition, positively and negatively correlated significant genes of E2F4 were identified in HCC. Pathway enrichment analyses revealed that the top 100 positively correlated significant genes of E2F4 were closely related to nuclear splicing and degradation-related pathways. Furthermore, nine hub genes correlated with E2F4 expression were validated based on a protein-protein interaction (PPI) network. It was also demonstrated that E2F4 expression was negatively correlated to immune purity and positively correlated to immune cell infiltration. E2F4 could serve as a novel biomarker for HCC diagnosis and prognosis prediction.
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http://dx.doi.org/10.7150/jca.51616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890309PMC
January 2021

DLX6-AS1 is a potential biomarker and therapeutic target in cancer initiation and progression.

Clin Chim Acta 2021 Jun 17;517:1-8. Epub 2021 Feb 17.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China. Electronic address:

Long noncoding RNAs (lncRNAs) are involved in multiple functions such as the regulation of cellular homeostasis. They play prominent roles in the pathogenesis of human cancer, and contribute to every hallmark of cancer. The novel cancer-related lncRNA DLX6 antisense RNA 1 (DLX6-AS1) plays an essential regulatory role in enhancing and initiating carcinogenesis and tumor progression. This progression is due to the aberrant regulation of downstream factors in vitro as well as in vivo. DLX6-AS1 is significantly dysregulated in various cancers. DLX6-AS1 functions in tumor initiation and progression are regulated at the epigenetic, transcription, and posttranscriptional regulation levels. DLX6-AS1 functions as an oncogene, binding to miRNA targeting sites competing endogenous RNAs and causing the upregulation of downstream tumor-related genes and carcinogenesis. The regulation and detailed molecular mechanisms of DLX6-AS1 and its potential role in malignancies are comprehensively described in this paper. DLX6-AS1 has the potential to become a novel biomarker and therapeutic target for cancer.
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http://dx.doi.org/10.1016/j.cca.2021.02.006DOI Listing
June 2021

OpenAWSEM with Open3SPN2: A fast, flexible, and accessible framework for large-scale coarse-grained biomolecular simulations.

PLoS Comput Biol 2021 02 12;17(2):e1008308. Epub 2021 Feb 12.

Center for Theoretical Biological Physics, Rice University, Houston, Texas, United States of America.

We present OpenAWSEM and Open3SPN2, new cross-compatible implementations of coarse-grained models for protein (AWSEM) and DNA (3SPN2) molecular dynamics simulations within the OpenMM framework. These new implementations retain the chemical accuracy and intrinsic efficiency of the original models while adding GPU acceleration and the ease of forcefield modification provided by OpenMM's Custom Forces software framework. By utilizing GPUs, we achieve around a 30-fold speedup in protein and protein-DNA simulations over the existing LAMMPS-based implementations running on a single CPU core. We showcase the benefits of OpenMM's Custom Forces framework by devising and implementing two new potentials that allow us to address important aspects of protein folding and structure prediction and by testing the ability of the combined OpenAWSEM and Open3SPN2 to model protein-DNA binding. The first potential is used to describe the changes in effective interactions that occur as a protein becomes partially buried in a membrane. We also introduced an interaction to describe proteins with multiple disulfide bonds. Using simple pairwise disulfide bonding terms results in unphysical clustering of cysteine residues, posing a problem when simulating the folding of proteins with many cysteines. We now can computationally reproduce Anfinsen's early Nobel prize winning experiments by using OpenMM's Custom Forces framework to introduce a multi-body disulfide bonding term that prevents unphysical clustering. Our protein-DNA simulations show that the binding landscape is funneled towards structures that are quite similar to those found using experiments. In summary, this paper provides a simulation tool for the molecular biophysics community that is both easy to use and sufficiently efficient to simulate large proteins and large protein-DNA systems that are central to many cellular processes. These codes should facilitate the interplay between molecular simulations and cellular studies, which have been hampered by the large mismatch between the time and length scales accessible to molecular simulations and those relevant to cell biology.
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http://dx.doi.org/10.1371/journal.pcbi.1008308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906472PMC
February 2021

HAND2-AS1: A functional cancer-related long non-coding RNA.

Biomed Pharmacother 2021 May 5;137:111317. Epub 2021 Feb 5.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China. Electronic address:

Long non-coding RNAs (lncRNAs) regulate gene expression and carcinogenesis. The lncRNA heart and neural crest derivatives expressed transcript 2 antisense RNA 1 (HAND2‑AS1) suppresses tumor growth, and its expression level was lower in tumor tissues than in adjacent normal tissues of most types of human cancers, including non-small cell lung cancer, ovarian cancer, breast cancer, gastric cancer, colorectal cancer, cervical cancer, endometrial cancer, prostate cancer, and esophagus squamous cell carcinoma. However, one study reported that the HAND2‑AS1 expression was upregulated in hepatocellular carcinoma tissues comparing with non-tumor tissues and it promoted tumor development. The aberrant expression of HAND2-AS1 was strongly linked to tumor progression and prognosis. Moreover, HAND2-AS1 was involved in tumor cell proliferation, differentiation, apoptosis, and cellular glucose metabolism. This review summarizes data on the expression profile, functions, underlying mechanism, and clinical value of HAND2-AS1 in cancer. The expression profile of HAND2-AS1 in 33 tumors was evaluated by bioinformatics analysis of The Cancer Genome Atlas.
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http://dx.doi.org/10.1016/j.biopha.2021.111317DOI Listing
May 2021

Progress and assessment of lncRNA DGCR5 in malignant phenotype and immune infiltration of human cancers.

Am J Cancer Res 2021 1;11(1):1-13. Epub 2021 Jan 1.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou 310003, China.

As a special type of noncoding RNA, long noncoding RNAs (lncRNAs) have vital roles during the development of human cancers and may be novel predictors or therapeutic targets for improving the management of patients with cancer. DiGeorge syndrome critical region gene 5 () is a prominent tumor-associated lncRNA, exerting tumor suppressor or oncogenic roles in various cancers. Previous studies have reported that has low expression in most types of cancers but high expression in triple-negative breast cancer, gallbladder cancer, and lung cancer. And expression is related to many hallmarks of cancer types, including cell proliferation, invasion, migration, apoptosis, stemness, and therapeutic responsiveness. Additionally, the pivotal molecules involved in DGCR5 regulation of signaling pathways are attributed to cancer hallmarks related to the pathogenesis of different types of malignant tumors. Herein, we discuss the DGCR5 expression pattern in various types of tumor tissues and relationships between DGCR5 expression and immune cell infiltration and immune purity. We also review our current understanding of DGCR5 in carcinogenesis and its potential application as a prognostic biomarker or therapeutic target in human cancers.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840720PMC
January 2021

Natural Killer T Cells in Various Mouse Models of Hepatitis.

Biomed Res Int 2021 6;2021:1782765. Epub 2021 Jan 6.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, China.

Natural killer T (NKT) cells are a key component of innate immunity. Importantly, a growing body of evidence indicates that NKT cells play an integral role in various acute and chronic liver injuries. NKT cells participate in the progression of an injury through the secretion of cytokines, which promote neutrophil infiltration and enhance Fas ligand (FasL) and granzyme-mediated NKT cytotoxic activity. Therefore, examining the role of NKT cells in hepatic disease is critical for a comprehensive understanding of disease pathogenesis and may provide insight into novel approaches for treatment. For more than a century, mouse models that imitate the physiopathological conditions of human disease have served as a critical tool in biological and medical basic research, including studies of liver disease. Here, we review the role of NKT cells in various mouse models of hepatitis.
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http://dx.doi.org/10.1155/2021/1782765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810568PMC
June 2021

The dual functions of the long noncoding RNA CASC15 in malignancy.

Biomed Pharmacother 2021 Mar 1;135:111212. Epub 2021 Feb 1.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China. Electronic address:

Emerging evidence has demonstrated that long noncoding RNAs (lncRNAs) play vital roles in tumorigenesis and progression. LncRNAs can participate in various biological processes, such as cell growth, anti-apoptosis functions, migration, and invasion. Cancer susceptibility candidate 15 (CASC15) is a cancer-related lncRNA that has been reported to play opposite roles in the pathogenesis of different types of cancers. Studies have shown that CASC15 is downregulated in ovarian cancer and neuroblastoma, acting mainly as a tumour suppressor, while it is highly expressed and carcinogenic in hepatocellular carcinoma (HCC), lung cancer, tongue squamous cell carcinoma, gastric cancer, colorectal cancer, cervical cancer, and breast cancer. Furthermore, aberrant CASC15 expression is associated with tumorigenesis, progression, and patient outcomes via regulation of target genes and signalling pathways. In this review, we summarize current data concerning the regulatory functions and underlying mechanisms of CASC15 in tumour development. We also highlight its potential clinical utility as a biomarker for early detection or as a therapeutic target in human cancers.
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http://dx.doi.org/10.1016/j.biopha.2020.111212DOI Listing
March 2021

Model based on five tumour immune microenvironment-related genes for predicting hepatocellular carcinoma immunotherapy outcomes.

J Transl Med 2021 01 6;19(1):26. Epub 2021 Jan 6.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, NO. 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.

Background: Although the tumour immune microenvironment is known to significantly influence immunotherapy outcomes, its association with changes in gene expression patterns in hepatocellular carcinoma (HCC) during immunotherapy and its effect on prognosis have not been clarified.

Methods: A total of 365 HCC samples from The Cancer Genome Atlas liver hepatocellular carcinoma (TCGA-LIHC) dataset were stratified into training datasets and verification datasets. In the training datasets, immune-related genes were analysed through univariate Cox regression analyses and least absolute shrinkage and selection operator (LASSO)-Cox analyses to build a prognostic model. The TCGA-LIHC, GSE14520, and Imvigor210 cohorts were subjected to time-dependent receiver operating characteristic (ROC) and Kaplan-Meier survival curve analyses to verify the reliability of the developed model. Finally, single-sample gene set enrichment analysis (ssGSEA) was used to study the underlying molecular mechanisms.

Results: Five immune-related genes (LDHA, PPAT, BFSP1, NR0B1, and PFKFB4) were identified and used to establish the prognostic model for patient response to HCC treatment. ROC curve analysis of the TCGA (training and validation sets) and GSE14520 cohorts confirmed the predictive ability of the five-gene-based model (AUC > 0.6). In addition, ROC and Kaplan-Meier analyses indicated that the model could stratify patients into a low-risk and a high-risk group, wherein the high-risk group exhibited worse prognosis and was less sensitive to immunotherapy than the low-risk group. Functional enrichment analysis predicted potential associations of the five genes with several metabolic processes and oncological signatures.

Conclusions: We established a novel five-gene-based prognostic model based on the tumour immune microenvironment that can predict immunotherapy efficacy in HCC patients.
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http://dx.doi.org/10.1186/s12967-020-02691-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788940PMC
January 2021

Mitochondrial Mechanisms of Necroptosis in Liver Diseases.

Int J Mol Sci 2020 Dec 23;22(1). Epub 2020 Dec 23.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.

Cell death represents a basic biological paradigm that governs outcomes and long-term sequelae in almost every hepatic disease. Necroptosis is a common form of programmed cell death in the liver. Necroptosis can be activated by ligands of death receptors, which then interact with receptor-interactive protein kinases 1 (RIPK1). RIPK1 mediates receptor interacting receptor-interactive protein kinases 3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL) and necrosome formation. Regarding the molecular mechanisms of mitochondrial-mediated necroptosis, the RIPK1/RIPK3/MLKL necrosome complex can enhance oxidative respiration and generate reactive oxygen species, which can be a crucial factor in the susceptibility of cells to necroptosis. The necrosome complex is also linked to mitochondrial components such as phosphoglycerate mutase family member 5 (PGAM5), metabolic enzymes in the mitochondrial matrix, mitochondrial permeability protein, and cyclophilin D. In this review, we focus on the role of mitochondria-mediated cell necroptosis in acute liver injury, chronic liver diseases, and hepatocellular carcinoma, and its possible translation into clinical applications.
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http://dx.doi.org/10.3390/ijms22010066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793526PMC
December 2020

Exploring the F-actin/CPEB3 interaction and its possible role in the molecular mechanism of long-term memory.

Proc Natl Acad Sci U S A 2020 09 26;117(36):22128-22134. Epub 2020 Aug 26.

Center for Theoretical Biological Physics, Rice University, Houston, TX 77005;

Dendritic spines are tiny membranous protrusions on the dendrites of neurons. Dendritic spines change shape in response to input signals, thereby strengthening the connections between neurons. The growth and stabilization of dendritic spines is thought to be essential for maintaining long-term memory. Actin cytoskeleton remodeling in spines is a key element of their formation and growth. More speculatively, the aggregation of CPEB3, a functional prion that binds RNA, has been reported to be involved in the maintenance of long-term memory. Here we study the interaction between actin and CPEB3 and propose a molecular model for the complex structure of CPEB3 and an actin filament (F-actin). The results of our computational modeling, including both energetic and structural analyses, are compared with novel data from peptide array experiments. Our model of the CPEB3/F-actin interaction suggests that F-actin potentially triggers the aggregation-prone structural transition of a short CPEB3 sequence by zipping it into a beta-hairpin form. We also propose that the CPEB3/F-actin interaction might be regulated by the SUMOylation of CPEB3, based on bioinformatic searches for potential SUMOylation sites as well as SUMO interacting motifs in CPEB3. On the basis of these results and the existing literature, we put forward a possible molecular mechanism underlying long-term memory that involves CPEB3's binding to actin, its aggregation, and its regulation by SUMOylation.
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http://dx.doi.org/10.1073/pnas.2012964117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486757PMC
September 2020

Immune checkpoint targeting TIGIT in hepatocellular carcinoma.

Am J Transl Res 2020 15;12(7):3212-3224. Epub 2020 Jul 15.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou, Zhejiang, China.

Hepatocellular carcinoma (HCC) has an extremely poor prognosis and is one of the most common malignancies worldwide. Immune checkpoint suppression has become the most effective treatment option for liver cancer. The strategies used for immune checkpoint inhibitor targeting cancer therapies have been affected by some significant successes, including blocking the advanced-stage malignant tumor by death protein 1 (PD-1)/programmed cell death ligand (PDL-1), and cytotoxic T-lymphocyte antigen-4 (CTLA4) pathways. T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) is an immune checkpoint that participates in tumor immune surveillance. Mainly expressed on T cells, natural killer (NK) cells, and other antigen-presenting cells (APCs), it diminishes cytokine production and exhibits strong suppressive properties. TIGIT achieves a more active antitumor immune response and highlights a pivotal role for cancer immunotherapy. Preclinical studies have found inhibitory effects using a targeted approach. Monotherapy targeting TIGIT or in combination with anti-PD-1/PD-L1 monoclonal antibodies for the treatment of patients with advanced solid malignancies have demonstrated improved antitumor immune responses. Due to the high tumor heterogeneity of liver cancer, immune checkpoint suppression therapy still needs further exploration. Therefore, we provide insights into the characteristics of TIGIT and the immune system in HCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407725PMC
July 2020

Predictors for the progression of hepatic cirrhosis to hepatocellular carcinoma under long-term antiviral therapy.

Eur J Gastroenterol Hepatol 2020 03;32(3):447-453

Department of Infectious Disease.

Objective: Patients diagnosed with hepatitis B virus (HBV)-related hepatic cirrhosis have the potential for progression to hepatocellular carcinoma (HCC) even while undergoing long-term nucleos(t)ide analog (NA) therapy. This study investigated the predictors for the progression of hepatic cirrhosis to HCC under long-term NA therapy.

Methods: This retrospective study enrolled 898 patients diagnosed with HBV-related hepatic cirrhosis. They received NA therapy between January 2012 and January 2015. The values for the liver stiffness measurement (LSM), laboratory tests, and disease history were collected. The diagnostic specificity of the serum, was assessed with a receiver operating characteristic curve.

Results: The overall 2- and 3-year cumulative incidence of HCC was 6.8% and 15.15%, respectively. The LSM values were higher in the patients who had progressed to HCC. The serum PIVKA-II levels were more efficient than the serum AFP levels for the diagnosis of early HCC as the larger area under curve (0.866 vs. 0.687). The multivariate logistic regression analysis showed that HCC occurrence was significantly associated with the baseline LSM value (odds ratio = 1.035). At the end of the study, the death rate for the patients with larger LSM values was higher than that for those with lower LSM values (67.88% vs. 39.90%).

Conclusion: Patients with HBV-related cirrhosis have the potential for progression to HCC even under long-term NA therapy. The LSM value and the serum PIVKA-II level are significant predictors of HCC occurrence.
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http://dx.doi.org/10.1097/MEG.0000000000001631DOI Listing
March 2020

Nitrogen and Boron Dual-Doped Graphene Quantum Dots for Near-Infrared Second Window Imaging and Photothermal Therapy.

Appl Mater Today 2019 Mar 6;14:108-117. Epub 2018 Dec 6.

Department of Materials Science and Engineering, University of Washington, Seattle 98195, United States.

Fluorescence imaging of biological systems in the second near-infrared window (NIR-II) has recently drawn much attention because of its negligible background noise of autofluorescence and low tissue scattering. Here we present a new NIR-II fluorescent agent, graphene quantum dots dual-doped with both nitrogen and boron (N-B-GQDs). N-B-GQDs have an ultra-small size (~ 5 nm), are highly stable in serum, and demonstrate a peak fluorescent emission at 1000 nm and high photostability. In addition to the NIR-II imaging capability, N-B-GQDs efficiently absorb and convert NIR light into heat when irradiated by an external NIR source, demonstrating a photothermal therapeutic effect that kills cancer cells in vitro and completely suppresses tumor growth in a glioma xenograft mouse model. N-B-GQDs demonstrate a safe profile, prolonged blood half-life, and rapid excretion in mice, which are the characteristics favorable for in vivo biomedical applications.
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http://dx.doi.org/10.1016/j.apmt.2018.11.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752708PMC
March 2019

Biconcave Carbon Nanodisks for Enhanced Drug Accumulation and Chemo-Photothermal Tumor Therapy.

Adv Healthc Mater 2019 04 11;8(8):e1801505. Epub 2019 Mar 11.

Department of Materials Science and Engineering, University of Washington, Seattle, Washington, DC, 98195, USA.

It is considered a significant challenge to construct nanocarriers that have high drug loading capacity and can overcome physiological barriers to deliver efficacious amounts of drugs to solid tumors. Here, the development of a safe, biconcave carbon nanodisk to address this challenge for treating breast cancer is reported. The nanodisk demonstrates fluorescent imaging capability, an exceedingly high loading capacity (947.8 mg g , 94.78 wt%) for doxorubicin (DOX), and pH-responsive drug release. It exhibits a higher uptake rate by tumor cells and greater accumulation in tumors in a mouse model than its carbon nanosphere counterpart. In addition, the nanodisk absorbs and transforms near-infrared (NIR) light to heat, which enables simultaneous NIR-responsive drug release for chemotherapy and generation of thermal energy for tumor cell destruction. Notably, this NIR-activated dual therapy demonstrates a near complete suppression of tumor growth in a mouse model of triple-negative breast cancer when DOX-loaded nanodisks are administered systemically.
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http://dx.doi.org/10.1002/adhm.201801505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6483846PMC
April 2019

Ocular surface pathogenesis associated with precocious eyelid opening and necrotic autologous tissue in mouse with disruption of Prickle 1 gene.

Exp Eye Res 2019 03 24;180:208-225. Epub 2018 Dec 24.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 Xianlie South Road, Guangzhou 510060, China. Electronic address:

Ocular surface disease is one major type of eye diseases. Different etiologies trigger distinct pathological responses of the ocular surface. We previously reported that genetically engineered mice with ablation of Prickle 1 manifested precocious eyelid opening with ensuing cornea dysplasia. The current study aimed to characterize the molecular traits and the direct cause of ocular pathology associated with precocious eyelid opening in the Prickle 1 mutant mouse. Prickle 1 mutant mice exhibited a slew of ocular surface pathology including cell proliferation, cell fate transformation and inflammatory infiltration coinciding with the timing of the precocious eyelid opening. Forced eyelid opening in wild type mice did not induce cornea pathology comparable to that of the Prickle 1 mutants. Necrotic tissue debris was found associated with the lesioned cornea. RNAseq analysis of the mutant cornea revealed an expression profile shared by a range of dermatological diseases involving immune responses and cancer. Taken together, the data suggest that the necrotic eyelid debris plays an important role in ocular pathogenesis of the Prickle 1 mutant mouse, which may represent a type of non-infectious keratoconjunctivitis caused by damaged autologous tissues. Additionally, Prickle 1 mutant cornea pathogenesis may offer molecular insights into other types of epithelial pathogenesis.
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http://dx.doi.org/10.1016/j.exer.2018.12.012DOI Listing
March 2019

NIR-responsive carbon-based nanocarriers for switchable on/off drug release and synergistic cancer therapy.

J Mater Chem B 2018 Dec 6;6(47):7794-7799. Epub 2018 Nov 6.

Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, 210008, Jiangsu, P. R. China.

Herein, we present a light-switchable drug delivery system based on chitosan-gated carbon-based nanocarriers (CGC NCs) that exhibit a loading capacity for doxorubicin as high as ∼89.65 wt% and controlled on/off release with/without NIR irradiation. In vitro and in vivo results show that the CGC NCs manifest high efficacy for cancer therapy through a synergistic effect of combined chemo-photothermal treatment.
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http://dx.doi.org/10.1039/c8tb02398kDOI Listing
December 2018

Ubiquitin-Specific Peptidase 22 Contributes to Colorectal Cancer Stemness and Chemoresistance via Wnt/β-Catenin Pathway.

Cell Physiol Biochem 2018 18;46(4):1412-1422. Epub 2018 Apr 18.

Background/aims: Two major barriers to the successful treatment of colorectal cancer (CRC) are the development of stem cell-like characteristics (stemness) and chemoresistance. Ubiquitin-specific peptidase 22 (USP22) is a deubiquitinating enzyme and putative CRC marker that has emerged as a potential cause of both phenomena in CRC. There is evidence that USP22 acts through the Wnt/β-catenin pathway and that downregulation of the latter may reduce chemoresistance.

Methods: In this study, we used CRC tissue specimens from human patients as well as human CRC cell lines to evaluate the role of USP22 in CRC stemness and chemoresistance in vitro and in vivo. RT-PCR and western blot were used for gene expression analyses. Immunohistochemistry was performed for USP22 expression in clinical samples. CD133 levels were analyzed by flow cytometry. Sphere formation and MTT assays were used for self-renewal and proliferation analysis. Chemoresistance was evaluated by cell viability and sphere formation assays.

Results: We found a significant increase of USP22 in recurrent CRC and chemoresistant CRC cells as compared to primary CRC and non-chemoresistant CRC cells, respectively. We then demonstrated that USP22 mediates CRC cell chemoresistance through the Wnt/β-catenin pathway and that reducing USP22 in CRC cells diminishes chemoresistance.

Conclusions: Having established the crucial role of USP22 in CRC stemness and chemoresistance, this study suggests that USP22 may be an ideal genetic target in the treatment of chemoresistant CRC.
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http://dx.doi.org/10.1159/000489156DOI Listing
July 2018

Dose selection of central or peripheral administration of sufentanil affect opioid induced cough?: a prospective, randomized, controlled trial.

BMC Anesthesiol 2018 04 10;18(1):38. Epub 2018 Apr 10.

Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China.

Background: Opioid-induced cough (OIC) is one of the most common complications of opioids during anesthesia induction. This study was designed to assess the incidence of OIC mediated by different intravenous route.

Methods: A total of 102(ASA I-II) scheduled for elective surgery under general anesthesia were randomly allocated into two groups: central vein group (group CV, n = 51) and peripheral vein group (group PV, n = 51). The incidence, onset time and severity of OIC were evaluated within 1 min just after sufentanil injection during induction. Meanwhile, heart rate (HR) and blood pressure (BP) were also recorded to assess the hemodynamic changes.

Results: The incidence of OIC was 10/51 (20.4%) in group CV and 16/51 (32%) in group PV, patients received central venous administration of sufentanil experienced less OIC compared with those injected by peripheral venous route (P < 0.05), as well as a significantly lower incidence of severe OIC (P < 0.05). Nevertheless, the onset of OIC and hemodynamic data were comparable between two groups (P > 0.05).

Conclusion: Our study indicates that sufentanil administration by central venous route reduces the incidence and severity of OIC, but without significant changes in hemodynamic status.

Trial Registration: Chinese Clinical Trial Registry with registration number ChiCTR-IOR-15006075 . Registered 28 February 2015.
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http://dx.doi.org/10.1186/s12871-018-0502-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5894202PMC
April 2018

A Spatiotemporal Requirement for Prickle 1-Mediated PCP Signaling in Eyelid Morphogenesis and Homeostasis.

Invest Ophthalmol Vis Sci 2018 02;59(2):952-966

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Purpose: Tissue closure/fusion is a fundamental process during organogenesis, driven in part by the Wnt/planar cell polarity (Wnt/PCP) pathway. This study explored the spatial and temporal aspects of PCP signaling in eyelid development through analysis of mice lacking Prickle 1, a core PCP component, and the Prickle1-dependent signaling networks underlying eyelid development.

Methods: Wild type and Prickle 1 compound mutant mice with a hypomorphic and a null allele were bred and used to study eyelid morphogenesis. The time course of embryonic eyelid fusion and postnatal reopening was examined by light microscopy of tissue sections and scanning electron microscopy. Immunohistochemistry was conducted to monitor cell proliferation, death, and molecular identities through pre- and postnatal eyelid development.

Results: Prickle 1 mutant embryos exhibited a profound delay in eyelid closure at embryonic ages, but manifested precocious eyelid reopening postnatally, with ensuing cornea malformation. Mutant embryonic showed downregulation of phosphorylated c-Jun, and upregulation of increased β-catenin in separate cell populations of the eyelid front area. Increased cell death and decreased mesenchymal infiltration was observed in postnatal mutant eyelid prior to eyelid reopening. While broadly expressed in many tissues, Prickle 1 was spatially restricted to the eyelid front at E15.5, a location where c-Jun and β-catenin expression was altered in Prickle 1 mutants.

Conclusions: The study demonstrates a spatiotemporal requirement for Prickle 1-mediated PCP signaling during eyelid morphogenesis and homeostasis. The study links Prickle 1-mediated PCP signaling to existing networks, and provides a useful animal model for studying congenital ocular surface diseases.
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http://dx.doi.org/10.1167/iovs.17-22947DOI Listing
February 2018

Effects of propofol and sevoflurane on perioperative immune response in patients undergoing laparoscopic radical hysterectomy for cervical cancer.

Medicine (Baltimore) 2016 Dec;95(49):e5479

Department of Anesthesiology, Xuzhou Central Hospital, The Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, Jiangsu Department of Anesthesiology, Affiliated Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Department of Anesthesiology, Xuzhou Women and Children's Health Care Hospital, Xuzhou, Jiangsu, China.

The aim of this study is to compare the effects of propofol and sevoflurane anesthesia on perioperative immune response in patients undergoing laparoscopic radical hysterectomy for cervical cancer.Sixty patients with cervical cancer scheduled for elective laparoscopic radical hysterectomy under general anesthesia were randomized into 2 groups. TIVA group received propofol induction and maintenance and SEVO group received sevoflurane induction and maintenance. Blood samples were collected at 30 min before induction (T0); the end of the operation (T1); and 24 h (T2), 48 h (T3), and 72 h (T4) after operation. The T lymphocyte subsets (including CD3+ cells, CD4+ cells, and CD8+ cells) and CD4+/CD8+ ratio, natural killer (NK) cells, and B lymphocytes were analyzed by flow cytometry.After surgery, all immunological indicators except CD8+ cells were significantly decreased in both groups compared to basal levels in T0, and the counts of CD3+ cells, CD4+ cells, NK cells, and the CD4+/CD8+ ratios were significantly lower in the SEVO groups than that in the TIVA group. However, the numbers of B cells were comparable at all the time points between 2 groups.Laparoscopic radical hysterectomy for cervical cancer is associated with postoperative lymphopenia. In terms of protecting circulating lymphocytes, propofol is superior to sevoflurane.
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http://dx.doi.org/10.1097/MD.0000000000005479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266001PMC
December 2016

Assessment of periodontal mechano-nociceptive function in healthy Chinese individuals.

Arch Oral Biol 2016 Nov 28;71:104-109. Epub 2016 Jul 28.

Section of Orofacial Pain and Jaw Function, School of Dentistry, Aarhus University, Aarhus, Denmark; Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden; Scandinavian Center for Orofacial Neurosciences (SCON), Sweden.

Objective: Few clinical techniques are available for the description of mechano-nociceptive function in human periodontal tissues. The objective of this study was to test a new technique for assessment of periodontal mechano-nociceptive function by direct application of controlled forces to the teeth and quantify site, side and gender differences in healthy individuals.

Design: Twenty healthy young adults (ten males and ten females) participated. A handheld pressure algometer was used to assess pressure pain threshold (PPT) on the maxillary and mandibular central incisors, canines and first premolars on the left and the right side from two directions: lateral and vertical. Statistical analysis was performed using analyses of variance (ANOVA) with repeated measures to compare data.

Results: There were significant gender differences of PPT for both lateral (P=0.007) and vertical (P=0.001) directions with lower thresholds in females (higher sensitivity) than in males. A significant site effect (P=0.002, P<0.001) was observed with less sensitivity at the first premolar compared to the anterior teeth. No significant right-to-left side differences (P=0.082) were found for the PPTs. There were significant PPT differences between maxillary and mandibular teeth (P=0.020, P=0.041,) and significant differences between lateral and vertical direction (P<0.001).

Conclusion: The novel application of PPTs directly to the teeth indicated an adequate and practical method with potential value for clinical assessment of painful conditions affecting the periodontal ligament.
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http://dx.doi.org/10.1016/j.archoralbio.2016.07.012DOI Listing
November 2016

Transient Pain Following Orthodontic Fixed Appliances Induces Sensitization of Gingival and Periodontal Tissues.

J Oral Facial Pain Headache Summer 2016;30(3):228-33

Aims: To evaluate the transient effects of orthodontic treatment on the mechanical detection threshold (MDT) and mechanical pain threshold (MPT) of the buccal attached gingiva and the pressure pain threshold (PPT) of the buccal attached gingiva and of the teeth in two directions (perpendicular and parallel).

Methods: A total of 20 patients (15 females and 5 males) aged 18 to 30 years participated in the study. Perceived pain on a 0- to 10-cm visual analog scale (VAS) and MDT, MPT, and PPT scores were evaluated at two time points at the masseter muscle, gingiva, teeth, and hand (control) prior to orthodontic treatment (T₀) and 24 hours after the first archwire placement (T₁). Mean values and SEMs were calculated for all continuous variables. The differences between T₀ and T₁ of MDT, MPT, and PPT were analyzed by means of a paired Student t test.

Results: The pain intensity as assessed on the VAS was 4.2 ± 1.8 cm. No significant changes in MDT or MPT were found at the hand and buccal attached gingiva (P > .06). The PPTs at the buccal attached gingiva of teeth 21, 23, 24, and 34, at teeth 21, 23, 24, and 34 (perpendicular) and at teeth 21 and 23 (parallel) were lower (ie, more sensitive) at T₁ compared with T₀ (P < .04).

Conclusion: This study indicates for the first time that pain following insertion of an archwire causes sensitization to blunt-pressure stimuli both in the attached gingiva and in the periodontal ligament. Quantitative assessment of mechanical sensitivity may provide more insights into procedural pain and allow for better monitoring and evaluation of the effects of orthodontic treatment in the future.
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http://dx.doi.org/10.11607/ofph.1646DOI Listing
January 2017

Test-retest reliability of a new technique with pressure algometry applied to teeth in healthy Chinese individuals.

Eur J Oral Sci 2016 06 28;124(3):259-65. Epub 2016 Mar 28.

Section of Orofacial Pain and Jaw Function, School of Dentistry, Aarhus University, Aarhus, Denmark.

Pressure pain thresholds (PPTs) have been shown to be useful measures of mechanical pain sensitivity in deep tissues. However, clinical methods for measuring mechanical allodynia or hyperalgesia in teeth have not been reported. The aim of this study was to assess the reliability of PPTs in periodontal ligament of healthy Chinese participants. Twenty healthy young adults participated. Pressure pain thresholds were measured at six teeth and in two directions. The tests included three consecutive trials, in two separate sessions, which were performed on the first day by one examiner. After 1-3 wk, an identical protocol was carried out by two examiners, also in two separate sessions. There were no significant differences between repeated measures for all teeth. The PPTs had excellent reliability with high intraclass coefficients (ICCs) across different sessions (ICC: 0.871-0.956), days (ICC: 0.879-0.951), and examiners (ICC: 0.845-0.950). Pressure pain thresholds applied to the teeth have excellent intra- and inter-examiner agreement in healthy participants. This method may be proposed as an easy and reliable technique to assess mechanical pain sensitivity (e.g. mechanical allodynia and hyperalgesia) in the periodontal ligament, which is associated with endodontic or periodontal conditions.
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http://dx.doi.org/10.1111/eos.12264DOI Listing
June 2016

Molecular network including eIF1AX, RPS7, and 14-3-3γ regulates protein translation and cell proliferation in bovine mammary epithelial cells.

Arch Biochem Biophys 2014 Dec 2;564:142-55. Epub 2014 Oct 2.

Key Laboratory of Agricultural Biological Functional Genes, Northeast Agricultural University, Harbin 150030, China. Electronic address:

14-3-3γ, an isoform of the 14-3-3 protein family, was proved to be a positive regulator of mTOR pathway. Here, we analyzed the function of 14-3-3γ in protein synthesis using bovine mammary epithelial cells (BMECs). We found that 14-3-3γ interacted with eIF1AX and RPS7 by 14-3-3γ coimmunoprecipitation (CoIP) and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight (MALDI-TOF/TOF) peptide mass fingerprinting analysis. These interactions of 14-3-3γ with eIF1AX and RPS7 were further confirmed by colocalization and fluorescence resonance energy transfer (FRET) analysis. We also found that methionine could promote protein synthesis and trigger the protein expression levels of 14-3-3γ, eIF1AX and RPS7. Analysis of overexpression and inhibition of 14-3-3γ confirmed that it positively affected the protein expression levels of eIF1AX, RPS7, Stat5 and mTOR pathway to promote protein synthesis and cell proliferation in BMECs. We further showed that overexpression of eIF1AX and RPS7 also triggered protein translation and cell proliferation. From these results, we conclude that molecular network including eIF1AX, RPS7, and 14-3-3γ regulates protein translation and cell proliferation in BMECs.
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http://dx.doi.org/10.1016/j.abb.2014.09.014DOI Listing
December 2014
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