Publications by authors named "Fangfang Song"

65 Publications

Association between low density lipoprotein cholesterol and all-cause mortality: results from the NHANES 1999-2014.

Sci Rep 2021 Nov 11;11(1):22111. Epub 2021 Nov 11.

Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, Key Laboratory of Breast Cancer Prevention and Therapy in Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Huanhu Xi Road, Tiyuan Bei, Hexi District, Tianjin, 300060, People's Republic of China.

The association between low density lipoprotein cholesterol (LDL-C) and all-cause mortality has been examined in many studies. However, inconsistent results and limitations still exist. We used the 1999-2014 National Health and Nutrition Examination Survey (NHANES) data with 19,034 people to assess the association between LDL-C level and all-cause mortality. All participants were followed up until 2015 except those younger than 18 years old, after excluding those who died within three years of follow-up, a total of 1619 deaths among 19,034 people were included in the analysis. In the age-adjusted model (model 1), it was found that the lowest LDL-C group had a higher risk of all-cause mortality (HR 1.708 [1.432-2.037]) than LDL-C 100-129 mg/dL as a reference group. The crude-adjusted model (model 2) suggests that people with the lowest level of LDL-C had 1.600 (95% CI [1.325-1.932]) times the odds compared with the reference group, after adjusting for age, sex, race, marital status, education level, smoking status, body mass index (BMI). In the fully-adjusted model (model 3), people with the lowest level of LDL-C had 1.373 (95% CI [1.130-1.668]) times the odds compared with the reference group, after additionally adjusting for hypertension, diabetes, cardiovascular disease, cancer based on model 2. The results from restricted cubic spine (RCS) curve showed that when the LDL-C concentration (130 mg/dL) was used as the reference, there is a U-shaped relationship between LDL-C level and all-cause mortality. In conclusion, we found that low level of LDL-C is associated with higher risk of all-cause mortality. The observed association persisted after adjusting for potential confounders. Further studies are warranted to determine the causal relationship between LDL-C level and all-cause mortality.
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http://dx.doi.org/10.1038/s41598-021-01738-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586008PMC
November 2021

Transcriptomic Analysis Identified Two Subtypes of Brain Tumor Characterized by Distinct Immune Infiltration and Prognosis.

Front Oncol 2021 15;11:734407. Epub 2021 Oct 15.

Tianjin Cancer Institute, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China.

Background: Brain tumor ranks as the most devastating cancer type. The complex tumor immune microenvironment prevents brain tumor from receiving therapeutic benefits. The purpose of this study was to stratify brain tumors based on their distinct immune infiltration signatures to facilitate better clinical decision making and prognosis prediction.

Methods: We developed a deep learning model to characterize immune infiltration from transcriptome. The developed model was applied to distill expression signatures of transcriptome of brain tumor samples. We performed molecular subtyping with the extracted expression signatures to unveil brain tumor subtypes. Computational methods, including gene set enrichment analysis, Kaplan-Meier survival and multivariate Cox regression analyses, were employed.

Results: We identified two distinctive subtypes (i.e. C1/2) of brain tumor featured by distinct immune infiltration signatures. The C1 subtype is characterized by protective immune infiltration signatures, including high infiltration of CD8+ T cells and activation of . The C2 subtype has an extensive infiltration of tumor-associated macrophages and microglia, and was enriched with immune suppressive, wound-healing, and angiogenic signatures. The C1 subtype had significantly better prognosis as compared with C2 (Log-rank test, HR: 2.5, 95% CI: 2.2 - 2.7; = 8.2e-78). This difference remained statistically significant (multivariate Cox model, HR: 2.2, 95% CI: 1.7 - 2.9; = 3.7e-10) by taking into account age, gender, recurrent/secondary status at sampling time, tumor grade, histology, radio-chemotherapy, mutation, methylation, and co-deletion of 1p and 19q. This finding was validated in six datasets. The C2 subtype of glioblastoma patients with mutation has poor survival analogous to those without mutation (Log-rank test, adjusted = 0.8), while C1 has favorable prognosis as compared with glioblastoma of C2 subtype with mutation (Log-rank test, adjusted = 1.2e-3) or without mutation (Log-rank test, adjusted = 1.3e-6).

Conclusions: We identified two distinctive subtypes of brain tumor with different immune infiltration signatures, which might be helpful as an independent prognosticator for brain tumor.
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http://dx.doi.org/10.3389/fonc.2021.734407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554158PMC
October 2021

Miscell: An efficient self-supervised learning approach for dissecting single-cell transcriptome.

iScience 2021 Nov 2;24(11):103200. Epub 2021 Oct 2.

Tianjin Cancer Institute, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Huanhu Xi Road, Tiyuan Bei, Hexi District, Tianjin 300060, China.

We developed Miscell, a self-supervised learning approach with deep neural network as latent feature encoder for mining information from single-cell transcriptomes. We demonstrated the capability of Miscell with canonical single-cell analysis tasks including delineation of single-cell clusters and identification of cluster-specific marker genes. We evaluated Miscell along with three state-of-the-art methods on three heterogeneous datasets. Miscell achieved at least comparable or better performance than the other methods by significant margin on a variety of clustering metrics such as adjusted rand index, normalized mutual information, and -measure score. Miscell can identify cell-type specific markers by quantifying the influence of genes on cell clusters via deep learning approach.
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http://dx.doi.org/10.1016/j.isci.2021.103200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8529514PMC
November 2021

Parity and risk of developing breast cancer according to tumor subtype: A systematic review and meta-analysis.

Cancer Epidemiol 2021 Dec 24;75:102050. Epub 2021 Oct 24.

Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology in Tianjin, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China. Electronic address:

Background: Clinical breast cancer subtypes are categorized basing on the expression of hormone receptors and overexpression of the human epidermal growth factor receptor 2 (HER2). It is still unclear whether parity impact the risk of different breast cancer subtypes.

Methods: We searched eight mainstream databases for published epidemiologic studies that assessed the relationship between parity and risk of breast cancer subtypes up to January 12, 2021. Parity number were unified into nulliparity and ever parity. The random-effects or fixed-effect models were used to calculate the pooled odds ratios (ORs) and 95% confidence intervals (CIs) among different subtypes. Restricted cubic spline analysis with four knots was applied to determine the relationship of parity number and risk of breast cancer subtypes.

Results: We pooled sixteen case-control and four cohort studies, and performed an analysis including 7795 luminal A, 3576 luminal B, 1794 HER2-overexpressing, and 5192 triple-negative breast cancer cases among 1135131 participants. The combined ORs for ever parity versus nulliparity indicated a 34% reduction in luminal A risk (OR=0.66, 95% CI: 0.56-0.78), and a 29% reduction in luminal B risk (OR=0.71, 95% CI: 0.63-0.81), there was no significant association in HER2-overexpressing or TNBC risk. In the dose-response analysis, we observed a potentially non-linear and gradually increasing protective relationship between the number of parity and luminal breast cancer risk.

Conclusions: The effect of parity on breast cancer seems to vary among breast tumor subtypes, and it plays a protective role in luminal breast cancer.
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http://dx.doi.org/10.1016/j.canep.2021.102050DOI Listing
December 2021

WNT7B overexpression rescues bone loss caused by glucocorticoids in mice.

FASEB J 2021 07;35(7):e21683

Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, MO, USA.

Glucocorticoids, widely prescribed for anti-inflammatory and immunosuppressive purposes, are the most common secondary cause for osteoporosis and related fractures. Current anti-resorptive and anabolic therapies are insufficient for treating glucocorticoid-induced osteoporosis due to contraindications or concerns of side effects. Glucocorticoids have been shown to disrupt Wnt signaling in osteoblast-lineage cells, but the efficacy for Wnt proteins to restore bone mass after glucocorticoid therapy has not been examined. Here by using two mouse genetic models wherein WNT7B expression is temporally activated by either tamoxifen or doxycycline in osteoblast-lineage cells, we show that WNT7B recovers bone mass following glucocorticoid-induced bone loss, thanks to increased osteoblast number and function. However, WNT7B overexpression in bone either before or after glucocorticoid treatments does not ameliorate the abnormal accumulation of body fat. The study demonstrates a potent bone anabolic function for WNT7B in countering glucocorticoid-induced bone loss.
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http://dx.doi.org/10.1096/fj.202100151RRDOI Listing
July 2021

Functional Interrogation of Enhancer Connectome Prioritizes Candidate Target Genes at Ovarian Cancer Susceptibility Loci.

Front Genet 2021 19;12:646179. Epub 2021 Mar 19.

Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China.

Identifying causal regulatory variants and their target genes from the majority of non-coding disease-associated genetic loci is the main challenge in post-Genome-Wide Association Studies (GWAS) functional studies. Although chromosome conformation capture (3C) and its derivative technologies have been successfully applied to nominate putative causal genes for non-coding variants, many GWAS target genes have not been identified yet. This study generated a high-resolution contact map from epithelial ovarian cancer (EOC) cells with two H3K27ac-HiChIP libraries and analyzed the underlying gene networks for 15 risk loci identified from the largest EOC GWAS. By combinatory analysis of 4,021 fine-mapped credible variants of EOC GWAS and high-resolution contact map, we obtained 162 target genes that mainly enriched in cancer related pathways. Compared with GTEx eQTL genes in ovarian tissue and annotated proximal genes, 132 HiChIP targets were first identified for EOC causal variants. More than half of the credible variants (CVs) involved interactions that were over 185 kb in distance, indicating that long-range transcriptional regulation is an important mechanism for the function of GWAS variants in EOC. We also found that many HiChIP gene targets showed significantly differential expressions between normal ovarian and EOC tumor samples. We validated one of these targets by manipulating the rs9303542 located region with CRISPR-Cas9 deletion and dCas9-VP64 activation experiments and found altered expression of HOXB7 and HOXB8 at 17q21.32. This study presents a systematic analysis to identify putative target genes for causal variants of EOC, providing an in-depth investigation of the mechanisms of non-coding regulatory variants in the etiology and pathogenesis of ovarian cancer.
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http://dx.doi.org/10.3389/fgene.2021.646179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017555PMC
March 2021

Nitrene-mediated intermolecular N-N coupling for efficient synthesis of hydrazides.

Nat Chem 2021 04 22;13(4):378-385. Epub 2021 Mar 22.

State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin, China.

N-N linkages are found in many natural compounds and endow fascinating structural and functional properties. In comparison to the myriad methods for the construction of C-N bonds, chemistry for N-N coupling, especially in an intermolecular fashion, remains underdeveloped. Here, we report a nitrene-mediated intermolecular N-N coupling of dioxazolones and arylamines under iridium or iron catalysis. These reactions offer a simple and efficient method for the synthesis of various hydrazides from readily available carboxylic acid and amine precursors. Although the Ir-catalysed conditions usually give higher N-N coupling yield than the Fe-catalysed conditions, the reactions of sterically more demanding dioxazolones derived from α-substituted carboxylic acids work much better under the Fe-catalysed conditions. Mechanistic studies revealed that the nitrogen atom of Ir acyl nitrene intermediates has strong electrophilicity and can undergo nucleophilic attack with arylamines with the assistance of Cl···HN hydrogen bonding to form the N-N bond with high efficiency and chemoselectivity.
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http://dx.doi.org/10.1038/s41557-021-00650-0DOI Listing
April 2021

SNPs within microRNA binding sites and the prognosis of breast cancer.

Aging (Albany NY) 2021 02 26;13(5):7465-7480. Epub 2021 Feb 26.

Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China.

Single nucleotide polymorphisms (SNPs) within microRNA binding sites can affect the binding of microRNA to mRNA and regulate gene expression, thereby contributing to cancer prognosis. Here we performed a two-stage study of 2647 breast cancer patients to explore the association between SNPs within microRNA binding sites and breast cancer prognosis. In stage I, we genotyped 192 SNPs within microRNA binding sites using the Illumina Goldengate platform. In stage II, we validated SNPs associated with breast cancer prognosis in another dataset using the TaqMan platform. We identified 8 SNPs significantly associated with breast cancer prognosis in stage I (<0.05), and only rs10878441 was statistically significant in stage II (AA vs CC, HR=2.21, 95% CI: 1.11-4.42, =0.024). We combined the data from stage I and stage II, and found that, compared with rs10878441 AA genotype, CC genotype was associated with poor survival of breast cancer (HR=2.19, 95% CI: 1.30-3.70, =0.003). Stratified analyses demonstrated that rs10878441 was related to breast cancer prognosis in grade II and lymph node-negative patients (<0.05). The Leucine-rich repeat kinase 2 (LRRK2) rs10878441 CC genotype is associated with poor prognosis of breast cancer in a Chinese population and may be used as a potential prognostic biomarker for breast cancer. • The LRRK2 rs10878441 CC genotype is associated with poor prognosis of breast cancer in a Chinese population. • Stratified analyses demonstrated that rs10878441 was related to breast cancer prognosis in grade II patients and lymph node-negative patients.
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http://dx.doi.org/10.18632/aging.202612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993692PMC
February 2021

An immunomodulatory signature of responsiveness to immune checkpoint blockade therapy.

Clin Transl Med 2020 Dec;10(8):e238

Tianjin Cancer Institute, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China.

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http://dx.doi.org/10.1002/ctm2.238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752154PMC
December 2020

Clinical Validation of Two Recombinase-Based Isothermal Amplification Assays (RPA/RAA) for the Rapid Detection of African Swine Fever Virus.

Front Microbiol 2020 21;11:1696. Epub 2020 Jul 21.

National Reference Laboratory for African Swine Fever, National Surveillance and Research Center for Exotic Animal Diseases, National Surveillance and Research Center for Exotic Animal Diseases, China Animal Health and Epidemiology Center, Qingdao, China.

African swine fever (ASF), caused by African swine fever virus (ASFV), is a devastating infectious disease of domestic pigs and wild boars, and has tremendous negative socioeconomic impact on the swine industry and food security worldwide. It is characterized as a notifiable disease by World Organisation for Animal Health (OIE). No effective vaccine or treatment against ASF has so far been available. Early detection and rapid diagnosis are of potential significance to control the spread of ASF. Recombinase-based isothermal amplification assay, recombinase polymerase amplification (RPA) developed by TwistDx (Cambridge, United Kingdom) or recombinase-aided amplification (RAA) by Qitian (Wuxi, China), is becoming a molecular tool for the rapid, specific, and cost-effective identification of multiple pathogens. In this study, we aim to investigate if RPA/RAA can be a potential candidate for on-site, rapid and primary detection of ASFV. A panel of 152 clinical samples previously well-characterized by OIE-recommended qPCR was enrolled in this study, including 20 weak positive (Ct value ≥ 30) samples. This panel was consisted of different types, such as EDTA-blood, spleen, lung, lymph node, kidney, tonsil, liver, brain. We evaluated two recombinase-based isothermal amplification assays, RPA or RAA, by targeting the ASFV gene (p72), and validated the clinical performance in comparison with OIE real-time PCR. Our result showed that the analytical sensitivity of RPA and RAA was as 93.4 and 53.6 copies per reaction, respectively at 95% probability in 16 min, at 39°C. They were universally specific for all 24 genotypes of ASFV and no cross reaction to other pathogens including Classical swine fever virus (CSV), Foot-and-mouth disease virus (FMDV), Pseudorabies virus, Porcine circovirus 2 (PCV2), Porcine Reproductive and respiratory syndrome virus (PPRSV). The results on detection of various kinds of clinical samples indicated an excellent diagnostic agreement between RPA, RAA and OIE real-time PCR method, with the kappa value of 0.960 and 0.973, respectively. Compared to real-time PCR, the specificity of both RPA and RAA was 100% (94.40% ∼ 100%, 95% CI), while the sensitivity was 96.59% (90.36% ∼ 99.29%, 95% CI) and 97.73% (92.03% ∼ 99.72%, 95% CI), respectively. Our data demonstrate that the developed recombinase-based amplification assay (RPA/RAA), promisingly equipped with field-deployable instruments, offers a sensitive and specific platform for the rapid and reliable detection of ASFV, especially in the resource-limited settings for the purpose of screening and surveillance of ASF.
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http://dx.doi.org/10.3389/fmicb.2020.01696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385304PMC
July 2020

Yes-associated protein promotes tumour necrosis factor α-treated cementoblast mineralization partly by inactivating NF-κB pathway.

J Cell Mol Med 2020 07 8;24(14):7939-7948. Epub 2020 Jun 8.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China.

Cementum regeneration, as one of the most difficult challenges of periodontal regeneration, is influenced by inflammatory factors. Inflammation may hamper or promote periodontal tissue repair under different circumstances, as it is found to do in dentin-pulp complex and bone tissue. Our team demonstrated that YAP promotes mineralization of OCCM, a cementoblast cell line. However, the effect of YAP on its mineralization under inflammatory microenvironment is unclear. In this study, cementogenesis in vitro was up-regulated after transient TNF-α treatment for 30 minutes. YAP expression also was increased by TNF-α treatment. YAP overexpression promoted OCCM mineralization after the cells were transiently treated with TNF-α because YAP overexpression inhibited NF-κB pathway activity, while YAP knockdown elevated it. The inhibited mineralization potential and activated NF-κB pathway activity by YAP knockdown also were partly rescued by the application of the NF-κB inhibitor Bay 11-7082. These results demonstrated that YAP plays a positive role in the mineralization of TNF-α transiently treated cementoblast, partly by inhibiting the NF-κB pathway activity.
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http://dx.doi.org/10.1111/jcmm.15426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348144PMC
July 2020

Tumor specific methylome in Chinese high-grade serous ovarian cancer characterized by gene expression profile and tumor genotype.

Gynecol Oncol 2020 07 1;158(1):178-187. Epub 2020 May 1.

Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, Tianjin, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China. Electronic address:

Objective: Extensive genetic and limited epigenetics have been characterized by the Cancer Genome Atlas (TCGA) among Western High-grade serous ovarian cancer (HGSOC). The present study aimed to characterize Chinese HGSOC at genome scale.

Methods: We used reduced representation bisulfite sequencing to investigate whole-genome and tumor-specific DNA methylation in 21 HGSOC tumors paired with their normal tissues, followed by a replication study involving additional 41 HGSOC patients. Altered methylation patterns in HGSOC were further characterized by gene expression profiles and whole-exome sequencing data.

Results: Comparing HGSOC tumors with normal tissues we observed global hypomethylation but with more specific hypermethylation in gene promoter. Totally, we revealed 159,881 differentially methylated regions (DMRs) and 4060 differentially expressed genes (DEGs). By integrating DNA methylation and mRNA expression data, we identified 153 negative (mainly in the upstream region) and 115 positive (mainly in the CDS regions) DMRs-DEGs correlated pairs, respectively. The negatively correlated DMRs-DEGs underlined Wnt and cell adhesion molecule binding as critical canonical pathways disrupted by DNA methylation. Eleven DMRs (in CAPS, FZD7, CDKN2A, PON3, KLF4, etc.), accompanied with a global DNA methylation marker, were validated in the replication samples. Whole-exome sequencing presented a relatively less dominated TP53 mutation in Chinese HGSOC compared to TCGA dataset. Unsupervised analysis of the three-level omics data identified differential methylation and expression subgroups based on tumor genetics, one of which presented increased DNA methylation and significantly associated with TP53 mutation.

Conclusions: Our individual and integrated analyses contribute details about the tissue-specific genetic and DNA methylation landscape of Chinese HGSOC.
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http://dx.doi.org/10.1016/j.ygyno.2020.04.688DOI Listing
July 2020

Inducible expression of Wnt7b promotes bone formation in aged mice and enhances fracture healing.

Bone Res 2020 3;8. Epub 2020 Feb 3.

2Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO 63110 USA.

There remain unmet clinical needs for safe and effective bone anabolic therapies to treat aging-related osteoporosis and to improve fracture healing in cases of nonunion or delayed union. Wnt signaling has emerged as a promising target pathway for developing novel bone anabolic drugs. Although neutralizing antibodies against the Wnt antagonist sclerostin have been tested, Wnt ligands themselves have not been fully explored as a potential therapy. Previous work has demonstrated Wnt7b as an endogenous ligand upregulated during osteoblast differentiation, and that Wnt7b overexpression potently stimulates bone accrual in the mouse. The earlier studies however did not address whether Wnt7b could promote bone formation when specifically applied to aged or fractured bones. Here we have developed a doxycycline-inducible strategy where Wnt7b is temporally induced in the bones of aged mice or during fracture healing. We report that forced expression of Wnt7b for 1 month starting at 15 months of age greatly stimulated trabecular and endosteal bone formation, resulting in a marked increase in bone mass. We further tested the effect of Wnt7b on bone healing in a murine closed femur fracture model. Induced expression of Wnt7b at the onset of fracture did not affect the initial cartilage formation but promoted mineralization of the subsequent bone callus. Thus, targeted delivery of Wnt7b to aged bones or fracture sites may be explored as a potential therapy.
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http://dx.doi.org/10.1038/s41413-019-0081-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997361PMC
February 2020

Tumor markers CA15-3, CA125, CEA and breast cancer survival by molecular subtype: a cohort study.

Breast Cancer 2020 Jul 10;27(4):621-630. Epub 2020 Feb 10.

Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Molecular Cancer Epidemiology, Tianjin Medical University Cancer Institute and Hospital, Huanhu Xi Road, Tiyuan Bei, Hexi District, Tianjin, 300060, People's Republic of China.

Background: The burden of breast cancer has grown rapidly in China during recent decades. However, the association between tumor markers (CA15-3, CA125, and CEA) and breast cancer survival among certain molecular subtypes is unclear; we described this association in a large, population-based study.

Methods: We conducted a cohort study including 10,836 women according to the Tianjin Breast Cancer Cases Cohort. Demographic and epidemiologic data were collected by a structured face-to-face questionnaire. Clinico-pathological parameters were abstracted from medical records, and follow-up information was obtained once a year by telephone. The primary endpoints were breast cancer-specific survival (BCSS) and disease-free survival (DFS). We utilized the Cox proportional hazard model to calculate hazard ratios (HRs) and 95% confidence intervals (CI).

Results: Among all patients, elevated CA15-3 and CEA exhibited consistently and statistically significant reduced BCSS compared with normal ones (CA15-3: HR 1.54, 95% CI 1.01-2.34; CEA: HR 2.45, 95% CI 1.40-4.30). Similar patterns of association were observed for DFS (CA15-3: HR 2.09, 95% CI 1.44-3.02; CEA: HR 2.71, 95% CI 1.71-4.27). Moreover, in luminal A subtype, high CA15-3 and CEA levels were associated with decreased BCSS (CA15-3: HR 4.47, 95% CI 2.04-9.81; CEA: HR 3.79, 95% CI 1.68-8.55) and DFS (CA15-3: HR 4.06, 95% CI 2.29-7.18, CEA: HR 3.41, 95% CI 1.75-6.64). In basal-like subtype, elevated CEA conferred reduction for BCSS (HR 5.13, 95% CI 1.65-15.9). However, no association was observed between CA125 and breast cancer outcome.

Conclusions: Preoperative CA15-3 and CEA levels differ in breast cancer molecular subtypes and yield strong prognostic information in Chinese women with breast cancer. Measuring CA15-3 and CEA levels before surgery may have the potential in predicting breast cancer survival and offering patients' personalized treatment strategy among luminal A and basal-like subtypes.
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http://dx.doi.org/10.1007/s12282-020-01058-3DOI Listing
July 2020

A Nomogram To Predict The Overall Survival Of Breast Cancer Patients And Guide The Postoperative Adjuvant Chemotherapy In China.

Cancer Manag Res 2019 28;11:10029-10039. Epub 2019 Nov 28.

Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer,Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China.

Purpose: We aim to construct a nomogram to predict breast cancer survival and guide postoperative adjuvant chemotherapy in China.

Patients And Methods: A total of 5,504 breast cancer patients from the Tianjin Breast Cancer Cases Cohort were included. Multivariable Cox regression was used to investigate the factors associated with overall survival (OS) and a nomogram was constructed based on these prognostic factors. The nomogram was internal and external validated and the performance was evaluated by area under the curve (AUC) and calibration curve. The partial score was also constructed and stratified them into low, moderate and high-risk subgroups for death according to the tripartite grouping method. Multivariate Cox regression analysis and the propensity score matching method were respectively used to test the association between adjuvant chemotherapy and OS in different risk subgroups.

Results: Age, diameter, histological differentiation, lymph node metastasis, estrogen, and progesterone receptor were incorporated into the nomogram and validation results showed this nomogram was well-calibrated to predict the 3-year [AUC =74.1%; 95% confidence interval (CI): 70.1-78.0%] and 5-year overall survival [AUC =72.3%; 95% CI: 69.6-75.1%]. Adjuvant chemotherapy was negatively associated with death in high risk subgroup [Hazard Ratio (HR) = 0.54; 95% CI: 0.37-0.77; <0.001]. However, no significant association were found in groups with low (HR=1.47; 95% CI: 0.52-4.19; =0.47) and moderate risk (HR=0.78; 95% CI: 0.42-1.48; =0.45). The 1:1 PSM generated 822 pairs of well-matched patients and Kaplan-Meier showed the high-risk patients could benefit from chemotherapy, whereas low risk and moderate risk subjects did not appear to benefit from chemotherapy.

Conclusion: Not all of the breast cancer patients benefit equally from chemotherapy. The nomogram could be used to evaluate the overall survival of breast cancer patients and predict the magnitude of benefit and guide adjuvant chemotherapy for breast cancer patients after surgery.
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http://dx.doi.org/10.2147/CMAR.S215000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886546PMC
November 2019

Detection rate is not higher for women with BBD history in breast cancer screening.

J Public Health (Oxf) 2021 06;43(2):333-340

Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Molecular Cancer Epidemiology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P. R. China.

Background: To investigate whether women with benign breast disease (BBD) history have higher breast cancer detection rate in screening.

Methods: We reviewed data for 33 001 female participants in Multi-modality Independent Screening Trial (MIST). Corresponding data for 6823 breast cancer patients were retrieved from the Tianjin Breast Cancer Cases Cohort (TBCCC) and analyzed for comparison.

Results: The breast cancer detection rate was 2.83‰ among women with BBD history and 3.28‰ in women without. Moreover, the proportion of carcinoma in situ (CIS) was also lower in women with BBD history than women without (7.69 versus 20.31%). In contrast, analysis of TBCCC data revealed a higher proportion of CIS in patients with BBD history (5.05%) than patients without (3.26%). Our data showed that a larger proportion of women with BBD history had undergone previous breast examinations. Additionally, among participants diagnosed with both breast cancer and BBD in MIST, we found a lower proportion of CIS in women with BBD history (11.76%) compared to women without (32.14%).

Conclusions: Women with BBD history were not found to have higher detection rate in breast cancer screening. Women with BBD history were more likely to be proactive in seeking breast examinations and to have breast cancer be diagnosed in clinic.
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http://dx.doi.org/10.1093/pubmed/fdz147DOI Listing
June 2021

Distance perception warped by social relations: Social interaction information compresses distance.

Acta Psychol (Amst) 2020 Jan 18;202:102948. Epub 2019 Nov 18.

Department of Psychology, Ningbo University, Ningbo, China; Center of Group Behavior and Social Psychological Service, Ningbo University, Ningbo, China.

Though distance perception feeds the fundamental input that constructs a visual structure of the world, the suggestion has been made that it is constrained by this constructed structure. Instead of focusing on the physically defined structure, this study investigates whether and how social relations, especially the quality of social interaction (how individuals interact) rather than its content (what type of social interaction), precisely influences distance perception. The quality of social interaction was framed as an actor's intent and incurred outcome regarding another individual, whether helpful or harmful. Through visual animations, intent was operationalized as an agent's (i.e., actor's) intentional or unintentional act having an influence on another agent (i.e., affectee). Two experiments were conducted. In Experiment 1, the act was helpful, resulting in small or great beneficial consequences to the affectee. In Experiment 2, the act was harmful and resulted in small or great losses to the affectee. We found that when the help or harm had a large effect on others (the great-benefits or great-losses conditions), distance was perceived as shorter than when help or harm was minor, and the actor's intent did not affect distance perception. This suggests that, regardless of the type of social interaction, distance perception is mainly influenced by the outcome of an act not by the actor's intent. It implies that the perceived quality of social interaction creates a social constraint on distance perception. These findings are consistent with the idea that the intent and outcome of an action are assessed differently, and they help us understand how social relation penetrates the perceptual system.
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http://dx.doi.org/10.1016/j.actpsy.2019.102948DOI Listing
January 2020

Cationic supercapacitance of carbon nanotubes covered with copper hexacyanoferrate.

Nanotechnology 2019 Dec 28;30(50):505401. Epub 2019 Aug 28.

Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, College of Life Sciences and Chemistry, Zhejiang Normal University, Jinhua, Zhejiang, 321004, People's Republic of China.

Carbon nanotubes (CNT) are uniformly covered with copper hexacyanoferrate (CuHCF) via coprecipitation to form a core shell structure. The CuHCF thickness can be tuned from 10 nm to 30 nm by changing the CuHCF loading in the hybrids from 25% to 58%. The capacitive behavior is affected by the hydrated cation radius. In 1 mol l KCl solution, CuHCF/CNT hybrids (46% CuHCF loading) show the largest specific capacitance of up to 989 F g at a discharge density of 1 A g. The hybrids also possess superior rate capability with only 8.2% capacitance loss when increasing the discharge current from 1 to 20 A g. The superior capacitive performance of the hybrids in the K-ion solution can be attributed to the smaller hydrated radius of the K ion, which will favor the diffusion of the cation within the CuHCF lattice, leading to a larger faradic current. Besides, the cyclic stability of the hybrids is surprising, with 89.7% capacitance retention after 10000 discharge/charge cycles. The CuHCF/CNT hybrids are combined with the reduced graphene oxides (RGOs) to construct an asymmetrical supercapacitor, and its potential window can reach up to 2.0 V. More importantly, this supercapacitor exhibits a high energy density of 60.4 Wh kg at the power density of 0.5 kW kg.
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http://dx.doi.org/10.1088/1361-6528/ab3ef2DOI Listing
December 2019

Rhodium(iii)-catalyzed diverse [4 + 1] annulation of arenes with 1,3-enynes sp/sp C-H activation and 1,4-rhodium migration.

Chem Sci 2019 Apr 26;10(14):3987-3993. Epub 2019 Feb 26.

Henan Key Laboratory of Organic Functional Molecule and Drug Innovation , School of Chemistry and Chemical Engineering , Henan Normal University , Xinxiang 453007 , China.

Nitrogen-rich heterocyclic compounds have a profound impact on human health. Despite the numerous synthetic methods, diversified, step-economic, and general synthesis of heterocycles remains limited. C-H bond functionalization catalyzed by rhodium(iii) cyclopentadienyls has proven to be a powerful strategy in the synthesis of diversified heterocycles. Herein we describe rhodium(iii)-catalyzed sp and sp C-H activation-oxidative annulations between aromatic substrates and 1,3-enynes, where alkenyl-to-allyl 1,4-rhodium(iii) migration enabled the generation of electrophilic rhodium(iii) π-allyls remote C-H functionalization. Subsequent nucleophilic trapping of these species by various sp-hybridized N-nucleophiles delivered three classes (external salts, inner salts, and neutral azacycles) of five-membered azacycles bearing a tetrasubstituted saturated carbon center, as a result of [4 + 1] annulation with the alkyne being a one-carbon synthon. All the reactions proceeded under relatively mild conditions with broad substrate scope, high efficiency, and excellent regioselectivity. The synthetic applications of this protocol have also been demonstrated, and experimental studies have been performed to support the proposed mechanism.
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http://dx.doi.org/10.1039/c9sc00545eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457175PMC
April 2019

NAC-loaded electrospun scaffolding system with dual compartments for the osteogenesis of rBMSCs in vitro.

Int J Nanomedicine 2019 23;14:787-798. Epub 2019 Jan 23.

Center for Smart Materials and Devices, State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, Hubei, China,

Purpose: In this study, we aimed to develop a unique -acetyl cysteine (NAC)-loaded polylactic-co-glycolic acid (PLGA) electrospun system with separate compartments for the promotion of osteogenesis.

Materials And Methods: We first prepared solutions of NAC-loaded mesoporous silica nanoparticles (MSNs), PLGA, and NAC in , -dimethylformamide and tetrahydrofuran for the construction of the electrospun system. We then fed solutions to a specific injector for electrospinning. The physical and chemical properties of the scaffold were characterized through scanning electron microscopy, transmission electron microscopy, and Fourier transform infrared spectroscopy. The release of NAC and Si from different PLGA scaffolds was estimated. The cell viability, cell growth, and osteogenic potential of rat bone marrow-derived stroma cell (rBMSCs) on different PLGA scaffolds were evaluated through MTT assay, live/dead staining, phalloidin staining, and Alizarin red staining. The expression levels of osteogenic-related markers were analyzed through real-time PCR (qRT-PCR).

Results: NAC was successfully loaded into MSNs. The addition of MSNs and NAC decreased the diameters of the electrospun fibers, increased the hydrophilicity and mechanical property of the PLGA scaffold. The release kinetic curve indicated that NAC was released from (PLGA + NAC)/([email protected]) in a biphasic pattern, that featured an initial burst release stage and a later sustained release stage. This release pattern of NAC encapsulated on the (PLGA + NAC)/([email protected]) scaffolds enabled to prolong the high concentrations of release of NAC, thus drastically affecting the osteogenic differentiation of rBMSCs.

Conclusion: A PLGA electrospun scaffold was developed, and MSNs were used as separate nanocarriers for recharging NAC concentration, demonstrating the promising use of (PLGA + NAC)/([email protected]) for bone tissue engineering.
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http://dx.doi.org/10.2147/IJN.S183233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361317PMC
March 2019

Comparison of breast cancer risk factors among molecular subtypes: A case-only study.

Cancer Med 2019 04 14;8(4):1882-1892. Epub 2019 Feb 14.

Key Laboratory of Breast Cancer Prevention and Therapy in Ministry of Education, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China.

Epidemiological studies have a clear definition of the risk factors for breast cancer. However, it is unknown whether the distribution of these factors differs among breast cancer subtypes. We conducted a hospital-based case-only study consisting of 8067 breast cancer patients basing on the Tianjin Cohort of Breast Cancer Cases. Major breast cancer subtypes including luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched and basal-like were defined by estrogen receptor, progesterone receptor, HER2, and Ki-67 status. Variables including demographic characteristics, reproductive factors, lifestyle habits, imaging examination, and clinicopathologic data were collected for patients. Chi-square test and one-way analysis of variance were used to compare the distributions of variables among the four breast cancer subtypes. Multivariate logistic regression was used to estimate the odds ratios and associated 95% confidence intervals where luminal A patients served as the reference group. Overall, more commonality rather than heterogeneity on the distributions of factors was found between the four molecular subtypes of breast cancer. The proportion of overweight and obesity were lower in HER2-enriched subtype. Women with age at menarche ≤13 years were more likely to be found in basal-like subtype. Postmenopausal women were more frequent in HER2-enriched and basal-like subtypes. Women with benign breast disease and higher breast density were more common in HER2-enriched subtype. Risk factor scoring showed that total risk scores were similar among the four subtypes. HER2-enriched and basal-like subtypes were more frequently diagnosed with large tumors. Calcification was more likely to be found in luminal B and HER2-enriched subtypes, whereas less distributed in basal-like subtype. Most of the breast cancer risk factors were similarly distributed among the four major breast cancer subtypes; commonality is predominant.
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http://dx.doi.org/10.1002/cam4.2012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488156PMC
April 2019

H19 and Foxc2 synergistically promotes osteogenic differentiation of BMSCs via Wnt-β-catenin pathway.

J Cell Physiol 2019 08 11;234(8):13799-13806. Epub 2019 Jan 11.

Department of Geriatrics, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.

Objective: To investigate the mechanism of H19 on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs).

Methods: Ovariectomized (OVX) mouse model was established. RNA immunoprecipitation and RNA pull-down assays were performed to determine the correlation between H19 and forkhead box C2 (Foxc2). Chromatin immunoprecipitation assay was used to identify whether Foxc2 binds to the Wnt4 promoter region. Molecules expressions were measured by quantitative real-time polymerase chain reaction and western blot.

Results: We found that H19 expression was reduced in the serum of patients with postmenopausal osteoporosis and BMSCs of OVX mice, and overexpression of H19 promoted osteogenic differentiation of BMSCs. Additionally, Foxc2 could bind to the Wnt4 promoter and promote its transcription. We also showed that H19 could bind to Foxc2, and H19/Foxc2 regulated Wnt promoter expression in a synergistic fashion, and H19/Foxc2 regulated osteogenic differentiation of BMSCs through Wnt-β-catenin pathway.

Conclusion: H19 and Foxc2 synergistically promoted osteogenic differentiation of BMSCs via Wnt-β-catenin pathway.
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http://dx.doi.org/10.1002/jcp.28060DOI Listing
August 2019

Insulin-Like Growth Factor-1 Alleviates Expression of Aβ and α-, β-, and γ-Secretases in the Cortex and Hippocampus of APP/PS1 Double Transgenic Mice.

J Mol Neurosci 2018 Dec 9;66(4):595-603. Epub 2018 Nov 9.

Department of General Practice, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, Heilongjiang, People's Republic of China.

To examine the effect of subcutaneous injection of insulin-like growth factor-1 (IGF-1) on the expression of the amyloid protein (Aβ), α-secretase (ADAM10), β-secretase (BACE1), and γ-secretase (PS1) in APP/PS1 double transgenic mice. APP/PS1 double transgenic mice and wild-type mice were divided into wild-type group, wild-type therapy group, transgenome group, and transgenic therapy group. Subcutaneous injection of IGF-1 (50 μg/kg day) was administered once daily to the wild-type therapy group and transgenic therapy group for 8 weeks, respectively. The expression of the Aβ in the cortex and hippocampus was detected by immunohistochemistry 8 weeks after administration. The levels of Aβ, DAM10, BACE1, and PS1 were analysed by Western blot. The expression of the Aβ in the cortex of the gene therapy group was significantly lower than that of the transgenome group (p < 0.05). In APP/PS1 double transgenic mice, BACE1 expression was markedly higher in both the hippocampus (p < 0.001, p = 0.00009) and the cortex (p = 0.001), compared to that of the wild-type mice. The treatment of IGF-1 markedly reduced ADAM10 expression in the hippocampus in both transgenic mice and wild-type mice (p < 0.05), whereas the treatment mainly decreased BACE1 expression in transgenic mice but not in the wild-type mice (p < 0.05). No significant differences in PS1 levels were detected in all groups. IGF decreased Aβ over-expression in the cortex and hippocampus and might inhibit the damage induced by Aβ in APP/PS1 double transgenic mice. Our study suggests that IGF-1 should inhibit Aβ production through α-secretase and β-secretase but not γ-secretase.
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http://dx.doi.org/10.1007/s12031-018-1201-4DOI Listing
December 2018

SIRT6 overexpression inhibits cementogenesis by suppressing glucose transporter 1.

J Cell Physiol 2019 04 7;234(4):4005-4014. Epub 2018 Sep 7.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education (KLOBM), School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China.

Cementum, which shares common features with bone in terms of biochemical composition, is important for the homeostasis of periodontium during periodontitis and orthodontic treatment. Sirtuin 6 (SIRT6), as a member of the sirtuin family, plays key roles in the osteogenic differentiation of bone marrow mesenchymal stem cells. However, the involvement of SIRT6 in cementoblast differentiation and mineralization and the underlying mechanisms remain unknown. In this study, we observed that the expression of SIRT6 increased during cementoblast differentiation initially. Analysis of the gain- and loss-of-function indicated that overexpressing SIRT6 in OCCM-30 cells suppresses cementoblast differentiation and mineralization and downregulating SIRT6 promotes cementogenesis. GLUT1, a glucose transporter necessary in cementogenesis, was inhibited by SIRT6. Overexpressing GLUT1 in SIRT6-overexpressed OCCM-30 cells rescued the inhibitory effect of SIRT6 on cementoblast differentiation and mineralization. Moreover, AMPK was activated after overexpressing SIRT6 and inhibited cementoblast differentiation and mineralization. Downregulating the expression of SIRT6 inhibited AMPK activity. Meanwhile, GLUT1 overexpression significantly decreased AMPK activity. Overall, on one hand, SIRT6 inhibited cementoblast differentiation and mineralization by suppressing GLUT1. On the other hand, SIRT6 inhibited cementoblast differentiation and mineralization by activating the AMPK pathway. GLUT1 overexpression also rescued the increased AMPK pathway activated by SIRT6.
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http://dx.doi.org/10.1002/jcp.27213DOI Listing
April 2019

IRX5 promotes NF-κB signalling to increase proliferation, migration and invasion via OPN in tongue squamous cell carcinoma.

J Cell Mol Med 2018 May 15. Epub 2018 May 15.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education (KLOBM), School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China.

Iroquois homeobox gene 5 (Irx5) is a highly conserved member of the Iroquois homeobox gene family. Members of this family play distinct and overlapping roles in normal embryonic cell patterning and development of malignancies. In this study, we observed that IRX5 was abnormally abundant in tongue squamous cell carcinoma (TSCC) tissues and cell lines. We used gain- and loss-of-function methods to overexpress and knockdown IRX5 expression in the TSCC cell line CAL27. Our results elucidated that elevated levels of IRX5 promoted proliferation, migration and invasion of TSCC cells, whereas stable or transient knockdown of IRX5 expression suppressed TSCC cell proliferation, migration and invasion. As a transcription factor, IRX5 performed this function by targeting osteopontin (OPN) promoter and activating the NF-κB pathway. Finally, studies in xenograft tumour model showed that IRX5 significantly enhanced OPN expression and promoted tumour growth. Taken together, our study elucidates a promotive effect of IRX5 in TSCC through the connection with OPN. These findings reveal the new molecular mechanism of TSCC, which may potentiate its use as a novel molecular therapy target for TSCC.
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http://dx.doi.org/10.1111/jcmm.13664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050492PMC
May 2018

Influence of naringenin on the biofilm formation of Streptococcus mutans.

J Dent 2018 09 18;76:24-31. Epub 2018 Apr 18.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory for Oral Biomedical Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China. Electronic address:

Objectives: To evaluate the effect of naringenin on the biofilm formation of Streptococcus mutans (S. mutans), and to investigate its mechanisms of action and biological toxicity.

Methods: Minimum inhibitory concentrations, growth curves, and biofilm inhibition rates of naringenin were determined to assess its antimicrobial effect on S. mutans. The morphology of S. mutans and the structure of biofilm were observed by FESEM and CLSM. Bacterial aggregation, bacterial surface hydrophobicity, and real-time PCR for gtfB, gtfC, comD, comE, and luxS mRNA expression were assessed to preliminarily investigate the mechanisms of action. MTT test using human dental pulp cells (HDPCs) was also performed to investigate cytotoxicity.

Results: The S.mutans growth curves, FESEM, CLSM showed that both 100 and 200 μg/mL of naringenin obviously inhibited S. mutans growth and biofilm formation, increased S. mutans surface hydrophobicity, reduced bacterial aggregation, and downregulated the mRNA expression of gtfB, gtfC, comD, comE, and luxS. However, naringenin at 200 μg/mL slightly decreased the growths of HDPCs compared with 100 μg/mL.

Conclusion: Naringenin at 100 and 200 μg/mL suppressed the second (bacterial adhesion) and third stages (biofilm maturation) of S. mutans biofilm formation.

Clinical Significance: Naringenin is promising for dental clinic promotion to prevent the biofilm formation of S. mutans, serving as a safe anti-caries agent at an appropriate concentration.
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http://dx.doi.org/10.1016/j.jdent.2018.04.013DOI Listing
September 2018

Application of electrophoretic deposition to occlude dentinal tubules in vitro.

J Dent 2018 04 31;71:43-48. Epub 2018 Jan 31.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China. Electronic address:

Objectives: This study aims to apply electrophoretic deposition (EPD) for occlusion of dentinal tubules in vitro and investigate its effect on tubule occlusion and shear bond strength (SBS).

Methods: Charged mesoporous silica nanoparticles (MSNs) were synthesized and characterized through field-emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), and Fourier transform infrared (FT-IR) spectroscopy analyses. Thirty-nine sensitive dentin specimens were modeled and assigned randomly to three groups with different treatments (n = 13 each): group 1, immersion in the MSN suspension; and groups 2 and 3, anodic EPD with the specimen on the negative and positive electrode respectively. The effect of dentinal tubule occlusion was evaluated by dentin permeability test (n = 10 each) and FESEM examination (n = 3 each). Moreover, 18 specimens were grouped (n = 6 each) and treated in the same method. A resin stick was bonded onto each of the specimen using a self-etch adhesive (single bond universal) for SBS testing.

Results: Negatively-charged MSNs were synthesized and characterized as small and well-dispersed particles. After the EPD treatment (group 3), the dentinal tubules were effectively occluded by MSNs, which infiltrated into the tubules at a depth of approximately 7-8 μm and tightly associated with the tubular inwalls. SBS was not significantly different among the three groups (P > 0.05).

Conclusions: Synthesized MSNs were deposited into dentinal tubules by EPD treatment without compromising dentin bond strength.

Clinical Significance: Application of EPD is a new approach for occlusion of dentinal tubules and exhibits potential in the study of dentin hypersensitivity.
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http://dx.doi.org/10.1016/j.jdent.2018.01.012DOI Listing
April 2018

The Role of Pannexin3-Modified Human Dental Pulp-Derived Mesenchymal Stromal Cells in Repairing Rat Cranial Critical-Sized Bone Defects.

Cell Physiol Biochem 2017 13;44(6):2174-2188. Epub 2017 Dec 13.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education (KLOBM), School & Hospital of Stomatology, Wuhan University, Wuhan, China.

Background/aims: Human dental pulp-derived mesenchymal stromal cells (hDPSCs) are promising seed cells for tissue engineering due to their easy accessibility and multi-lineage differentiation. Pannexin3 (Panx3) plays crucial roles during bone development and differentiation. The aim of the present study was to investigate the effect of Panx3 on osteogenesis of hDPSCs and the underlying mechanism.

Methods: Utilizing qRT-PCR, Western blot, and immunohistochemistry, we explored the change of Panx3 during osteogenic differentiation of hDPSCs. Next, hDPSCs with loss (Panx3 knockdown) and gain (Panx3 overexpression) of Panx3 function were developed to investigate the effects of Panx3 on osteogenic differentiation of hDPSC and the underlying mechanism. Finally, a commercial β-TCP scaffold carrying Panx3-modified hDPSCs was utilized to evaluate bone defect repair.

Results: Panx3 was upregulated during osteogenic differentiation in a time-dependent manner. Panx3 overexpression promoted osteogenic differentiation of hDPSCs, whereas depletion of Panx3 resulted in a decline of differentiation, evidenced by upregulated expression of mineralization-related markers, increased alkaline phosphatase (ALP) activity, and enhanced ALP and Alizarin red staining. Panx3 was found to interact with the Wnt/β-catenin signaling pathway, forming a negative feedback loop. However, Wnt/β-catenin did not contribute to enhancement of osteogenic differentiation as observed in Panx3 overexpression. Moreover, Panx3 promoted osteogenic differentiation of hDPSCs via increasing ERK signaling pathway. Micro-CT and histological staining results showed that Panx3-modified hDPSCs significantly improved ossification of critical-sized bone defects.

Conclusion: These findings suggest that Panx3 is a crucial modulator of hDPSCs differentiation.
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http://dx.doi.org/10.1159/000486023DOI Listing
March 2018

Yes-associated protein 1 promotes the differentiation and mineralization of cementoblast.

J Cell Physiol 2018 Mar 25;233(3):2213-2224. Epub 2017 Sep 25.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China.

Yes-associated protein 1 (YAP1) transcriptional coactivator is a mediator of mechanosensitive signaling. Cementum, which covers the tooth root surface, continuously senses external mechanical stimulation. Cementoblasts are responsible for the mineralization and maturation of the cementum. However, the effect of YAP1 on cementoblast differentiation remains largely unknown. In this study, we initially demonstrated that YAP1 overexpression enhanced the mineralization ability of cementoblasts. YAP1 upregulated the mRNA and protein expression of several cementogenesis markers, such as alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and dentin matrix acidic phosphoprotein 1 (DMP1). The YAP1 overexpression group showed higher intensities of ALP and Alizarin red stain than the YAP1-knockdown group. Unexpectedly, a sharp increase in the expression of dentin sialophosphoprotein (DSPP) was induced by the overexpression of YAP1. Knockdown of YAP1 suppressed DSPP transcriptional activity. YAP1 overexpression activated Smad-dependent BMP signaling and slightly inhibited Erk1/2 signaling pathway activity. Treatment with specific BMP antagonist (LDN193189) prevented the upregulation of the mRNA levels of ALP, RUNX2, and OCN, as well as intensity of ALP-stained and mineralized nodules in cementoblasts. The Erk1/2 signaling pathway inhibitor (PD 98,059) upregulated these cementogenesis markers. Thus, our study suggested that YAP1 enhanced cementoblast mineralization in vitro. YAP1 exerted its effect on the cementoblast partly by regulating the Smad-dependent BMP and Erk1/2 signaling pathways.
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http://dx.doi.org/10.1002/jcp.26089DOI Listing
March 2018

Geography of Food Consumption Patterns between South and North China.

Foods 2017 May 5;6(5). Epub 2017 May 5.

Department of Nutritional Science and Food Management, Ewha Womans University, Daehyun-dong, Sodaemun-gu, Seoul 03760, Korea.

The geographical environment, food culture, and dietary habits are substantially different between the southern and northern regions in China. We investigated the associations with dietary patterns and metabolic syndrome between Chinese adult from the southern and northern regions (North: 1249; South: 1849) using data from the Chinese Health and Nutrition 2009 survey. Respectively, four dietary patterns were identified by factor analysis in each of the two regions. Using factor analysis, each dietary pattern of factor score was calculated for three groups by tertile (T1 < T2 < T3). In the northern region, the association between the Alcohol and Western pattern and the risk of abdominal obesity (OR: 1.31; 95%: 1.01, 1.68) (OR: Odds Ratio), hypertriglyceridemia (OR: 1.35; 95%: 1.05, 1.74), high fasting blood glucose (OR: 1.37; 95%: 1.05, 1.80), and hypertension (OR: 1.55; 95%: 1.45, 1.99) was increased compared T1 to T3. In the southern region, the Convenience Food pattern was positively associated with hypertriglyceridemia (OR: 1.53; 95%: 1.03, 2.26), low high density lipoprotein (HDL)-cholesterol (OR: 1.96; 95%: 1.12, 3.43), and metabolic syndrome (OR: 1.79; 95%: 1.03, 3.11). The Alcohol dietary pattern was positively associated with high fasting blood glucose (OR: 1.83, 95%: 1.13, 2.97). There are some dietary pattern differences in the two regions. It is necessary to consider the factors of food culture and food intake habits in order to provide nutrition education to Chinese individuals from different regions in the future.
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http://dx.doi.org/10.3390/foods6050034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5447910PMC
May 2017
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