Publications by authors named "Yaofeng Jin"

19 Publications

  • Page 1 of 1

Breast cancer proliferation and deterioration-associated metabolic heterogeneity changes induced by exposure of bisphenol S, a widespread replacement of bisphenol A.

J Hazard Mater 2021 Feb 19;414:125391. Epub 2021 Feb 19.

State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong SAR, China. Electronic address:

Exposure to bisphenol A (BPA) is considered to be associated with the increased incidence of breast cancer. As a widespread replacement of BPA, the effect of bisphenol S (BPS) on breast tumor programming has not been studied. We reported that BPS exposure significantly promoted proliferation and deterioration of breast tumor by nonmonotonic dose response. The mechanisms were investigated by molecular biology and mass spectrometry-based lipidomics, proteomics and imaging. BPS exposure induced the spatially intratumor heterogeneity of morphology-driven lipids and proteins. The more significant proliferation resulted from BPS-10 (10 μg/kg body weight /day) exposure was evidenced by the variations of spatial distribution of lipids related to ceramide-sphingomyelin signaling pathway, proteins related to chromosomal stability and cell proliferation in central necrotic regions of breast tumor. In contrast, the BPS-100 exposure obviously accelerated deterioration of breast tumor by the variations of spatial distribution of proteins that were associated with the stability of nucleic acid structure in peripheral neoplastic regions. Accordingly, dysregulation of metabolism and protein function as well as DNA methylation and hypoxic tumor microenvironment could be applied to predict the possibility of tumorigenesis, proliferation and metastasis that might be caused by other bisphenol analogs.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125391DOI Listing
February 2021

Potential biomarkers Ang II/AT1R and S1P/S1PR1 predict the prognosis of hepatocellular carcinoma.

Oncol Lett 2020 Nov 8;20(5):208. Epub 2020 Sep 8.

Department of General Surgery, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.

Hepatocellular carcinoma (HCC) is one of the major causes of cancer-associated morbidity and mortality worldwide. Sphingosine-1-phosphate (S1P) and S1P receptor 1 (S1PR1) have been associated with the development and progression of HCC. Angiotensin II (Ang II) and Ang II receptor type 1 (AT1R) serve key roles in the progression and metastasis of HCC. However, the association and roles of Ang II/AT1R and S1P/S1PR1 in HCC have remained elusive. Therefore, the aim of the present study was to investigate the potential association between Ang II/AT1R and S1P/S1PR1 in HCC, as well as the association of AT1R and S1PR1 protein expression levels with the progression and prognosis of HCC. The results found that the serum levels of Ang II and S1P were significantly higher in patients with HCC compared with those in healthy donors. Furthermore, mRNA and protein levels of AT1R and S1PR1 were highly expressed in human HCC tissues. In addition, a positive correlation between Ang II/S1P and AT1R/S1PR1 in HCC was noted. Upregulation of AT1R and S1PR1 was associated with the progression of HCC. Patients with high AT1R and S1PR1 protein expression levels had unfavorable outcomes with respect to overall survival and recurrence-free survival compared with patients with low AT1R and S1PR1 expression levels. The present results demonstrated an association between AT1R and S1PR1 overexpression and the progression of HCC, indicating that Ang II/AT1R and S1P/S1PR may serve as valuable prognostic biomarkers for HCC.
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http://dx.doi.org/10.3892/ol.2020.12071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491028PMC
November 2020

miR-1323 suppresses bone mesenchymal stromal cell osteogenesis and fracture healing via inhibiting BMP4/SMAD4 signaling.

J Orthop Surg Res 2020 Jun 29;15(1):237. Epub 2020 Jun 29.

Department of Orthopedics, The Second Affiliated Hospital of Jiaxing University, No. 1518 Huanchengbei Road, Jiaxing, Zhejiang, 314299, China.

Background: Atrophic non-union fractures show no radiological evidence of callus formation within 3 months of fracture. microRNA dysregulation may underlie the dysfunctional osteogenesis in atrophic non-union fractures. Here, we aimed to analyze miR-1323 expression in human atrophic non-union fractures and examine miR-1323's underlying mechanism of action in human mesenchymal stromal cells.

Methods: Human atrophic non-union and standard healing fracture specimens were examined using H&E and Alcian Blue staining, immunohistochemistry, qRT-PCR, immunoblotting, and ALP activity assays. The effects of miR-1323 mimics or inhibition on BMP4, SMAD4, osteogenesis-related proteins, ALP activity, and bone mineralization were analyzed in human mesenchymal stromal cells. Luciferase reporter assays were utilized to assay miR-1323's binding to the 3'UTRs of BMP4 and SMAD4. The effects of miR-1323, BMP4, and SMAD4 were analyzed by siRNA and overexpression vectors. A rat femur fracture model was established to analyze the in vivo effects of antagomiR-1323 treatment.

Results: miR-1323 was upregulated in human atrophic non-union fractures. Atrophic non-union was associated with downregulation of BMP4 and SMAD4 as well as the osteogenic markers ALP, collagen I, and RUNX2. In vitro, miR-1323 suppressed BMP4 and SMAD4 expression by binding to the 3'UTRs of BMP4 and SMAD4. Moreover, miR-1323's inhibition of BMP4 and SMAD4 inhibited mesenchymal stromal cell osteogenic differentiation via modulating the nuclear translocation of the transcriptional co-activator TAZ. In vivo, antagomiR-1323 therapy facilitated the healing of fractures in a rat model of femoral fracture.

Conclusions: This evidence supports the miR-1323/BMP4 and miR-1323/SMAD4 axes as novel therapeutic targets for atrophic non-union fractures.
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http://dx.doi.org/10.1186/s13018-020-01685-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322887PMC
June 2020

Evaluation of the splenic injury following exposure of mice to bisphenol S: A mass spectrometry-based lipidomics and imaging analysis.

Environ Int 2020 02 12;135:105378. Epub 2019 Dec 12.

State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China. Electronic address:

Background: The widespread use of bisphenol A (BPA) substitutes has aroused great attention towards their toxicological evaluation in vivo and in vitro. Considering the intimate correlation between BPA and metabolic diseases, we explored whether bisphenol S (BPS), a major substitute to BPA, could cause the splenic toxicity by disturbing the lipid metabolism in mouse model.

Methods: We investigated the splenic injury by combing the mass spectrometry (MS)-based lipidomics and imaging analysis, as well as molecular biological methods. Mice were divided into three groups (control-olive oil, 10 and 100 μg-BPS/kg body weight/day group) and treated by BPS in 56 days.

Results: Two of BPS-treated concentrations induced the splenic morphological alterations and inflammation, including the decreased numbers and cellularity in the periarteriolar lymphoid sheath (T cell zone) and paucicellular primary lymphoid follicles (B cell zone) in splenic white pulp. Lipidome profiling of spleen after BPS treatment was also changed with up-regulated sphingosine [So], neutral glycosphingolipids [CerG], cholesteryl ester [ChE], diacylglycerols [DAG], lysophosphatidylcholine [LPC], lysophosphatidylethanolamine [LPE], phosphatidylglycerols [PG], phosphatidylinositols [PI] and phosphatidylserine [PS] as well as down-regulated ceramide [Cer], phosphatidylethanolamines [PE] and sphingomyelin [SM] compared to the control group. More importantly, significant different lipids in abundance and spatial distribution also implicated that white pulp were more sensitive to BPS treatment than other splenic sub-structures. Signaling lipids such as So (d18:0), Cer (d18:1/24:0), Cer (d18:1/22:0), SM (d18:1/22:1) and SM (d18:1/24:2) associated with inflammation were remarkable changed and co-localized in the splenic white pulp.

Conclusions: Our finding indicated that BPS exposure promoted the splenomegaly, pro-inflammatory activation and morphological alterations, as well as induced the lipidome perturbation in the immune cells of white pulp, which might be expected to contribute a new perspective of bisphenol-induced organ injury.
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http://dx.doi.org/10.1016/j.envint.2019.105378DOI Listing
February 2020

Distinct Microbial Populations Exist in the Mucosa-associated Microbiota of Diarrhea Predominant Irritable Bowel Syndrome and Ulcerative Colitis.

J Clin Gastroenterol 2019 10;53(9):660-672

Departments of Gastroenterology.

Goals: The goal of this study was to observe the bacterial colonization in the intestinal mucosa in the patients with diarrhea predominant irritable bowel syndrome (IBS-D) and ulcerative colitis (UC), and compare the mucosa-associated microbiota among the IBS-D patients, UC patients and the healthy control, and explore the correlation of the mucosa-associated microbiota with clinical manifestations.

Study: A total of 20 IBS-D patients, 28 patients with UC (16 active, 12 inactive) and 16 healthy subjects were enrolled in the study. They all underwent colonoscopies in the Gastrointestinal Endoscopy Center in the Second Affiliated Hospital of Xi'an Jiaotong University from June 2016 to October 2016. The mucosa specimens were taken at the junction of rectum and sigmoid colon for fluorescent in situ hybridization (FISH). Then the observed mucosa-associated microbiota was counted and compared.

Results: (1) In the IBS-D patients, the mucosa-associated bacteria were found to colonize in the surface of mucosa and the adjacent mucin layer. And in active UC, Escherichia coli, and Bacteroides were found in the lamina propria, in addition to bacterial colonization in the above-mentioned areas. (2) The total count of mucosa-associated bacteria and the individual counts of E. coli, Clostridium, and Bacteroides were significantly increased, and Bifidobacteria significantly decreased (P<0.05) in the IBS-D patients and UC patients. Counts of Lactobacillus were decreased only in UC patients compared with the healthy control. And a significantly larger variation of the above-mentioned bacterial counts was found in the patients with UC, particularly in those with active UC, compared with those with IBS-D (P<0.05); the counts in the UC group were 1.3 to 5.3 times more or less than those in the IBS-D group. (3) Compared with healthy controls and IBS-D, the total count of bacteria and the individual counts of E. coli and Bacteroides in the lamina propria in active UC were significantly increased (P<0.05). (4) A significant negative correlation of the counts of Lactobacillus and Bifidobacteria with the defecation frequency and fecal characteristics (P<0.05) was found in the IBS-D patients; in those with UC, both the total count of bacteria and the individual counts of E. coli, Clostridium, Bacteroides, Lactobacillus, and Bifidobacteria were significantly correlated, positively or negatively, with the related clinical manifestations and the activity of the disease (P<0.05).

Conclusions: Compared with the healthy control, intestinal microecology was changed most obviously in UC with much smaller differences though in the same direction in IBS-D. The translocation of some bacteria into the lamina propria was found in UC, particularly in active UC. The changes of mucosa-associated microbiota were related more or less to some clinical manifestations in IBS-D and UC.
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http://dx.doi.org/10.1097/MCG.0000000000000961DOI Listing
October 2019

Quantitative proteomics analysis of mitochondrial proteins in lung adenocarcinomas and normal lung tissue using iTRAQ and tandem mass spectrometry.

Am J Transl Res 2017 15;9(9):3918-3934. Epub 2017 Sep 15.

Department of Respiratory Medicine, Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'an 710004, Shaanxi Province, P. R. China.

Lung adenocarcinoma is the most common type of lung cancer. Unfortunately, lung adenocarcinoma has a poor prognosis and the pathogenesis remains unclear. Mitochondria are important mediators of tumorigenesis. However, the proteomics profile of lung adenocarcinoma mitochondrial proteins has not been elucidated. In this study, we investigated differences in the mitochondrial protein profiles between lung adenocarcinomas and normal tissue. Laser capture microdissection (LCM) was used to isolate the target cells from lung adenocarcinomas and normal tissue. The differential expression of mitochondrial proteins was determined using isobaric tags for relative and absolute quantitation (iTRAQ) combined with two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS). Bioinformatics analysis was performed using Gene Ontology and KEGG databases. As a result, 510 differentially expressed proteins were identified, 315 of which were upregulated and 195 that were downregulated. Of these proteins, 35.5% were mitochondrial or mitochondrial-related and were involved in binding, catalysis, molecular transduction, transport, and molecular structure. Based on the differentially expressed proteins, 63 pathways were significantly enriched through KEGG. The overexpression and cellular distribution of the mitochondrial protein C1QBP in the lung cancer samples was confirmed and verified by Western blotting. The relationship between C1QBP expression and clinicopathological features in lung cancer patients was likewise evaluated using immunohistochemistry, which revealed that the upregulation of C1QBP was associated with lymph node metastasis, pathological grade and clinical stage of TNM. The results indicate that the iTRAQ 2D-LC-MS/MS technique is a potential method for comparing mitochondrial protein profiles between tumor and normal tissue and could aid in identifying novel biomarkers and the mechanisms underlying carcinogenesis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622239PMC
September 2017

RAG2 involves the Igκ locus demethylation during B cell development.

Mol Immunol 2017 08 20;88:125-134. Epub 2017 Jun 20.

Department of Pathogenic Biology and Immunology, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of China, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, No.76 Yanta West Road, Xi'an, Shaanxi,710061, China. Electronic address:

The genes encoding the immunoglobulin κ light chain are assembled during B cell development by V(D)J recombination. For efficient rearrangement, the Igκ locus must undergo a series of epigenetic changes. One such epigenetic mark is DNA methylation. The mechanism that the Igκ locus is selectively demethylated at the pre-B cell stage has not previously been characterized. Here, we employed bisulfite DNA-modification assays to analyze the methylation status of the Igκ locus in primary pre-B cells from RAG-deficient mice with pre-rearranged Igh knock-in allele. We observed that the Igκ locus was hypermethylated in RAG2-deficient pre-B cells but hypomethylated in RAG1-deficient pre-B cells, indicating that wild-type (WT) RAG2 involves the Igκ locus demethylation in a RAG1-independent manner prior to rearrangement. We generated a series of RAG2 mutants between residue 350 and 383. We showed that these mutants mediated the Igκ rearrangement but failed to regulate the Igκ gene demethylation. We further analyzed that these mutants could increase RAG recombinase activity in vivo. We conclude that residues 350-383 region are responsible for endogenous Igκ locus demethylation at pre-B cells. We propose that WT RAG2 has an intrinsic function to regulate the Igκ locus demethylation.
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http://dx.doi.org/10.1016/j.molimm.2017.06.026DOI Listing
August 2017

Probiotics may delay the progression of nonalcoholic fatty liver disease by restoring the gut microbiota structure and improving intestinal endotoxemia.

Sci Rep 2017 03 28;7:45176. Epub 2017 Mar 28.

Department of Laboratory, The Second Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.

Gut-derived bacterial lipopolysaccharide (LPS) and subsequent hepatic toll-like receptor 4 (TLR4) activation have been recognized to be involved in the onset of diet-induced nonalcoholic fatty liver disease (NAFLD), but little is known about the variation of LPS and TLR4 during the progression of NAFLD. Probiotics were able to inhibit proliferation of harmful bacteria and improve gastrointestinal barrier function. However, it's unclear whether LPS/TLR4 is involved in the protection effect of probiotics on NAFLD. In this study, we described characteristic of gut microbiota structure in the progression of NAFLD, and we also analyzed the relationship between gut microbiota and LPS/TLR4 in this process. Furthermore, we applied probiotics intervention to investigate the effect of probiotics on gut flora structure, intestinal integrity, serum LPS, liver TLR4 and liver pathology. Our results showed that serum LPS and liver TLR4 were highly increased during progression of NAFLD, with gut flora diversity and gut mircobiological colonization resistance (B/E) declining. Furthermore, probiotics could improve gut microbiota structure and liver pathology. Probiotics could also downregulate serum LPS and liver TLR4. Our results suggested that both gut flora alteration and endotoxemia may be involved in the progression of NAFLD. Probiotics may delay the progression of NAFLD via LPS/TLR4 signaling.
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http://dx.doi.org/10.1038/srep45176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5368635PMC
March 2017

Association of a common variant of SYNPO2 gene with increased risk of serous epithelial ovarian cancer.

Tumour Biol 2017 Feb;39(2):1010428317691185

1 Department of Pathology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

In China, the majority of ovarian cancer patients (80%-90%) are women who are diagnosed with epithelial ovarian cancer. The SYNPO2 gene has recently been reported to be associated with epithelial ovarian cancer in Europeans. To investigate the association of common variants of SYNPO2 gene with epithelial ovarian cancer in Han Chinese individuals, we designed a case-control study with 719 epithelial ovarian cancer patients and 1568 unrelated healthy controls of Han Chinese descent. A total of 49 tagging single-nucleotide polymorphisms were genotyped; single-single-nucleotide polymorphism association, imputation, and haplotypic association analyses were performed. The single-nucleotide polymorphism rs17329882 was found to be strongly associated with serous epithelial ovarian cancer and with ages ≤49 years, consistent with the pre-menopausal status of analyzed epithelial ovarian cancer cases. Odds ratios and 95% confidence intervals provided evidence of the risk effects of the C allele of the single-nucleotide polymorphism on epithelial ovarian cancer. Imputation analyses also confirmed the results with a similar pattern. Additionally, haplotype analyses indicated that the haplotype block that contained rs17329882 was significantly associated with epithelial ovarian cancer risk, specifically with the serous epithelial ovarian cancer subtype. In conclusion, our results show that SYNPO2 gene plays an important role in the etiology of epithelial ovarian cancer, suggesting that this gene may be a potential genetic modifier for developing epithelial ovarian cancer.
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http://dx.doi.org/10.1177/1010428317691185DOI Listing
February 2017

Angiotensin II Enhances Proliferation and Inflammation through AT1/PKC/NF-κB Signaling Pathway in Hepatocellular Carcinoma Cells.

Cell Physiol Biochem 2016 07 20;39(1):13-32. Epub 2016 Jun 20.

Scientific Research Center, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.

Background/aims: The pathogenesis of hepatocellular carcinoma (HCC) is mainly characterized by persistent cycles of liver injury, inflammation, and compensatory hepatocyte proliferation. Angiotensin II (Ang II) behaves as an endogenous pro-inflammatory molecule playing a significant role in HCC, however, the molecular link between Ang II, proliferation and inflammation remains unclear.

Methods: Human HCC cell lines (HepG-2, SMMC-7721, MHCC97-H) were incubated with Ang II at the indicated concentrations for 24, 48, 72 h. MTT, BrdU ELISA, plate colony formation assay, immunohistochemistry, ELISA, small-interfering RNA(siRNA) transfection, quantitative real-time PCR and western blot were applied to assess their functional, morphological and molecular mechanisms in HCC cell lines.

Results: High expression of Ang II type 1 receptor (AT1) and low expression of AT2 in HCC cells and tissues were found. Next, Ang II could significantly enhance cell growth and proliferation. Albeit Ang II slightly increased the percentage of HCC cells in the G0/G1 phase using flow cytometry analysis, no statistically significant alterations were shown. Further studies suggested that Ang II could directly induce proliferation associated proteins C-myc and proliferating cell nuclear antigen (PCNA) expressions, and inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) productions in HCC cells. Interestingly, blocking AT1 and AT1 siRNA evidently inhibited Ang II-induced cell proliferation and inflammatory responses in HCC cells. More importantly, these effects may be mediated by AT1/PKC/NF-κB signaling pathway in HCC cell lines.

Conclusions: The results propose that Ang II/AT1/PKC/NF-κB signaling pathway is necessary for proliferation and inflammation of HCC cells, which increases our understanding of the pathogenesis and provides clues for developing new strategies against Ang II-related progress of HCC.
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http://dx.doi.org/10.1159/000445602DOI Listing
July 2016

MicroRNA-187 induces diffuse large B-cell lymphoma cell apoptosis via targeting BCL6.

Oncol Lett 2016 Apr 8;11(4):2845-2850. Epub 2016 Mar 8.

Department of Clinical Laboratory, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.

MicroRNAs (miRs) are endogenous non-coding RNAs that serve key functions in a wide range of biological processes, including cell growth, development, apoptosis and carcinogenesis. However, the association between miR-187 and B-cell lymphoma 6 (BCL6) has yet to be fully investigated in lymphoma cell apoptosis. The present study hypothesized that a post-translational mechanism may exist for BCL6 expression, which is regulated by miR-187 in lymphoma cells. The present study demonstrated that the expression of miR-187 in diffuse large B-cell lymphoma (DLBCL) cells was significantly decreased, and its expression was negatively correlated with BCL6 expression. It was also observed that miR-187 directly binds to the 3'-untranslated region of BCL6 mRNA and subsequently suppresses the expression of BCL6. Additionally, the induced expression of miR-187 significantly promoted DLBCL cell apoptosis . The drug sensitivity of human DLBCL SUDHL2 cells was increased following induction of miR-187 overexpression via an miR-187 mimic. In conclusion, the results of the present study suggest that the modulation of miR-187 expression in DLBCL cells may improve the sensitivity of chemotherapy through BCL6 targeting.
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http://dx.doi.org/10.3892/ol.2016.4313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4812283PMC
April 2016

TIGIT overexpression diminishes the function of CD4 T cells and ameliorates the severity of rheumatoid arthritis in mouse models.

Exp Cell Res 2016 Jan 9;340(1):132-8. Epub 2015 Dec 9.

Department of Immunology and Pathogenic Biology, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, China. Electronic address:

Rheumatoid arthritis (RA) is an immune-mediated disease with a pathogenesis that involves CD4 T cell activation. Multiple immune regulatory molecules expressed on CD4(+) T cells were involved in RA pathogenesis. In this study, we investigated the role of T cell immunoglobulin and ITIM (immunoreceptor tyrosine-based inhibition motif) domain (TIGIT) in RA. The frequency of TIGIT-positive CD4(+) T cells in the synovial fluid (SF) of active RA patients was lower than that of inactive RA patients. And a negative correlation between RA disease activity and TIGIT expression was found. In CD4(+) T cells isolated from SF of active RA patients, TIGIT upregulation significantly decreased cell proliferation, as shown by MTT assay. TIGIT overexpression also significantly decreased the production of IFN-γ and IL-17, and increased that of IL-10, as determined by ELISA and qRT-PCR. In CD4(+) T cells isolated from SF of inactive RA patients, TIGIT was silenced by siRNA transfection. As expected, TIGIT knockdown resulted in an opposite effect on cell proliferation and the production of cytokines, including IFN-γ, IL-17 and IL-10. A RA mouse model was established using type II collagen induction. TIGIT was upregulated in RA mouse by lentivector infection. As expected, TIGIT overexpression in vivo significantly alleviated the disease severity and deceased the levels of anti-collagen II antibodies. TIGIT upregulation in the early stage was more effective to alleviate disease severity. Our data suggested the potential therapeutic role of TIGIT in RA patients.
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http://dx.doi.org/10.1016/j.yexcr.2015.12.002DOI Listing
January 2016

MicroRNA-24 Regulates Osteogenic Differentiation via Targeting T-Cell Factor-1.

Int J Mol Sci 2015 May 21;16(5):11699-712. Epub 2015 May 21.

Department of Immunology and Pathogenic Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.

MicroRNAs (miRNAs) have been reported to have diverse biological roles in regulating many biological processes, including osteogenic differentiation. In the present study, we identified that miR-24 was a critical regulator during osteogenic differentiation. We found that overexpression of miR-24 significantly inhibited osteogenic differentiation, which decreased alkaline phosphatase activity, matrix mineralization and the expression of osteogenic differentiation markers. In contrast, inhibition of miR-24 exhibited an opposite effect. Furthermore, we delineated that miR-24 regulates post-transcriptionals of T-cell factor-1 (Tcf-1) via targeting the 3'-untranslated region (UTR) of Tcf-1 mRNA. MiR-24 was further found to regulate the protein expression of Tcf-1 in the murine osteoprogenitors cells and bone mesenchymal stem cells. Additionally, the positive effect of miR-24 suppression on osteoblast differentiation was apparently abrogated by Tcf-1 silencing. Taken together, our data suggest that miR-24 participates in osteogenic differentiation by targeting and regulating Tcf-1 expression in osteoblastic cells.
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http://dx.doi.org/10.3390/ijms160511699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463725PMC
May 2015

Impact of the IGFBP3 A-202C polymorphism on susceptibility and clinicopathologic features of breast cancer.

Biomed Pharmacother 2015 Apr 26;71:108-11. Epub 2015 Feb 26.

Department of Oncology, the Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, China.

Background: Insulin-like growth factor binding protein 3 (IGFBP3) plays an important role in cellular proliferation, differentiation, apoptosis, and mammary carcinogenesis. Genetic variations in IGFBP3 have been identified to influence the circulating IGFBP3 level. The present study determined the impact of an important promoter polymorphism (A-202C, rs2854744) on susceptibility and progression of breast cancer in a Chinese population.

Methods: We genotyped the IGFBP3 A-202C polymorphism in a case-control study involving 465 breast cancer patients and 799 age-matched, cancer-free controls using the TaqMan method. Logistic regression was used to assess the genetic association between the occurrence and progression of breast cancer.

Results: Compared with the wild genotype (-202AA), we found a statistically significant increased risk of breast cancer associated with the variant genotypes (CC vs. AA: OR=2.00, 95% CI=1.25-3.21; AC+CC vs. AA: OR=1.34, 95% CI=1.06-1.70). In the stratified analysis, the increased risk was more apparent among the subgroups of older subjects (OR=1.70, 95% CI=1.20-2.42). Furthermore, we found that patients carrying variant genotypes (AC+CC) had a significantly greater prevalence of large tumor size (OR=1.72, 95% CI=1.13-2.64; P=0.021).

Conclusion: Our results suggest that the functional IGFBP3 A-202C polymorphism may influence the susceptibility and progression of breast cancer in the Chinese population.
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http://dx.doi.org/10.1016/j.biopha.2015.02.018DOI Listing
April 2015

MiR-21 overexpression improves osteoporosis by targeting RECK.

Mol Cell Biochem 2015 Jul 17;405(1-2):125-33. Epub 2015 Apr 17.

Department of Orthopedics, The 1st Affiliated Hospital of Medical College, Xi'an Jiaotong University, 277 West Yanta Street, Xi'an, 710061, Shaanxi, China,

Osteoporosis is a kind of metabolic bone disorder. MicroRNA-21 (miR-21) has been proven to play an important role in bone formation, whereas its role in osteoporosis is unclear. In the present study, miR-21 expression was inhibited by TNF-α in mesenchymal stem cells (MSCs). TNF-α induced cell apoptosis, and inhibited cell proliferation and differentiation of MSCs. Whereas the effect was reversed by miR-21 mimics. Expression of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) which is a predicted target of miR-21 was inhibited by miR-21 mimics. A luciferase reporter gene assay showed that miR-21 directly bound to RECK 3'-UTR. The effect of TNF-α on MSCs was reversed by RECK siRNA which was consistent with miR-21 mimics. The expression of MT1-MMP was inhibited by TNF-α and enhanced by RECK siRNA and miR-21 mimics. For the in vivo study, an osteoporosis model (OVX) was established by bilateral oophorectomy in mice. The expression of miR-21 decreased and RECK increased in the OVX mice. When treated with lentiviral RECK shRNA, the osteocalcin concentration and alkaline phosphate activity of the OVX mice decreased. The bone mineral density of the right femur mid-diaphysis was improved by RECK shRNA. Collectively, miR-21 modulated the osteoporosis by targeting RECK. These results emphasize the role of miR-21 during osteoporosis and suggest RECK might be a new medical target for osteoporosis.
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http://dx.doi.org/10.1007/s11010-015-2404-4DOI Listing
July 2015

[A novel histological typing and grading-scale system of colorectal cancer].

Nan Fang Yi Ke Da Xue Xue Bao 2014 Feb;34(2):169-73

Department of Pathology, Second Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an 710004, China.E-mail:

Objective: To formulate a novel histological typing and grading-rated system for colorectal cancer (CRC) for evaluating the biological behavior of CRC and prognosis.

Methods: According to the highly heterogeneous histological features, WHO classification and histological differentiation criteria, and other biological behavior parameters of CRC, a novel histological typing and grading-scale system for CRC was designed. The histological typing and corresponding grading-scale of CRC was defined as the following: (1) No mucin-producing adenocarcinoma, including tubular adenocarcinoma, sieve-like acne adenocarcinoma, medullary carcinoma, serrated adenocarcinoma and micropapillary carcinoma, etc. (1-3 points); (2) Mucin-producing adenocarcinoma, including mucinous adenocarcinoma and signet ring cell carcinoma (3-4 points); (3) Squamous cell carcinoma (1-3 points); (4) Neuroendocrine tumors, including neuroendocrine tumors, neuroendocrine carcinoma (1-4 points); (5) The special type of CRC, including clear cell carcinoma, spindle cell carcinoma, etc. (4-points); (6) Undifferentiated carcinoma (5 points). The pathology report form was formatted based on the major histological type with the secondary histological type. The final total score of CRC was defined as the sum of the corresponding grading scores for different histological types. The total score of a single-structure CRC was defined as the corresponding grading score multiplied by 2. A total of 666 patients with advanced CRC were pathologically reviewed and analyzed to assess the correlation of the histological typing and grading scores with TNM staging and lymph node metastasis.

Results: The results showed a significant correlation of the histological grading-scale and TNM staging and lymph node metastasis (P<0.05). The scores of CRC histological grading-scale increased synchronously with the TNM staging and lymph node metastasis rate.

Conclusion: The novel histological grading system allows objective evaluation of the biological behaviors and prognosis of CRC for determining individualized postoperative treatment. This system still needs further revision and updates based on evidence from prospective, multi-centered, large-scale trials.
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February 2014

A genetic variant in the promoter of APE1 gene (-656 T>G) is associated with breast cancer risk and progression in a Chinese population.

Gene 2013 Nov 28;531(1):97-100. Epub 2013 Aug 28.

Department of Oncology, the Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, China. Electronic address:

Background/aims: APE1 is an important DNA repair protein in the base excision repair pathway. Genetic variations in APE1 have been suggested to influence individuals' susceptibility to human malignancies. The present study was aimed to investigate the associations between two functional polymorphisms in APE1 (-656T>G and 1349T>G) and breast cancer risk.

Methods: We genotyped the two polymorphisms in a case-control study of 500 breast cancer patients and 799 age-matched cancer-free controls using the TaqMan method. Unconditional logistic regression adjusted for potential confounding factors was used to assess the associations.

Results: We found that the variant genotypes of the -656T>G were significantly associated with decreased breast cancer risk, compared with the wild genotype [TG/GG vs. TT: adjusted odds ratio (OR)=0.71, 95% confidence interval (CI)=0.56-0.91], and the protective effect of this polymorphism was more predominant among the subgroups of younger subjects (<52 years) (OR=0.65, 95% CI=0.46-0.92). Besides, we found that the variant genotypes were associated with less frequent lymph node metastasis (P=0.020, OR=0.64, 95% CI=0.44-0.94). We did not observe any significant association between the 1349T>G polymorphism and breast cancer risk.

Conclusion: Our results suggest that the APE1 -656T>G but not the 1349T>G polymorphism may influence the susceptibility and progression of breast cancer in the Chinese population. Large population-based prospective studies are required to validate these findings.
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http://dx.doi.org/10.1016/j.gene.2013.08.052DOI Listing
November 2013

[Expression of TMEM16A in gastric carcinoma and its clinical implications].

Nan Fang Yi Ke Da Xue Xue Bao 2012 Jun;32(6):794-7

Department of Pathology, Second Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, China.

Objective: To investigate the expression of TMEM16A in gastric carcinoma and its clinical implications.

Methods: A total of 72 surgical specimens of gastric carcinoma were collected for examination of TMEM16A expression with immunohistochemical staining.

Results: TMEM16A expression was detected in the cytoplasm and cell membrane of the tumor cells. Of the 72 specimens of the tumor tissues, the total positivity rate of TMEM16A expression was 80.56% (58/72), significantly higher than the rate in the adjacent tissues (4.17%, 3/72, P<0.005).

Conclusion: Aberrant expression of TMEM16A occurs in the majority of gastric carcinoma cases. TMEM16A can be used as a new candidate target for diagnosis and treatment of gastric carcinoma.
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June 2012

A giant intrathoracic osteolipoma: A case report and review of the literature.

Int J Surg Case Rep 2012 30;3(7):290-2. Epub 2012 Mar 30.

Department of Pathology, Second Hospital of Medical School, Xian Jiaotong University, Xi'an, Shaanxi 710004, China.

Introduction: Lipomas are ubiquitous and can occur anywhere in the body. Intrathoracic lipomata are rare benign lesions. However, a complete removal giant intrathoracic osteolipoma is achieved with only 18 cases previous cases described in medical literature from 1960 to 2008.

Presentation Of Case: A 66-year-old female presented to our hospital suffered from mild chest pain and mild shortness of breath for more than 10 days. A subsequent chest X-ray and CT scans revealed a large homogeneous, low-attenuation fat density mass containing an oval calcification area in the center of the mass. Following surgical resection was performed successfully to remove the entire mass, which weighed a total of 1568g and measured 26cm×19cm×12cm in size. The histological analysis confirmed a giant intrathoracic osteolipoma without evidence of malignancy.

Discussion: Intrathoracic lipomas are rare, slow-growing benign tumors without any symptom, which originate from the adipose tissue in submesothelial layers of the pleura parietalis, diaphragm, mediastinal and extrapericardial. They may extend into the chest cavity and fully encapsulate in most cases. Chest X-ray and CT and MRI scans are the most helpful tests in the diagnosis of intrathoracic lipomas. Complete enbloc removal of lipoma whenever possible, is the only definitive treatment option and the only way to prevent future recurrences.

Conclusion: This case is the largest intrathoracic osteolipoma documented in the modern literature. Complete enbloc removal of lipoma whenever possible, is the only definitive treatment option.
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http://dx.doi.org/10.1016/j.ijscr.2012.03.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3356552PMC
October 2012