Publications by authors named "Fang-Fang Shen"

26 Publications

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and expression and association with the prognosis in esophageal squamous cell carcinoma.

Biomark Med 2020 10 7;14(15):1415-1426. Epub 2020 Sep 7.

Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

We investigated whether and were related to esophageal squamous cell carcinoma (ESCC). ESCC microarray datasets and reverse transcriptase qualitative PCR were used to analyze and expression. The GSE120356 and GSE33810 datasets identified and as the candidates and and expression was downregulated in ESCC. and were positively correlated with ESCC. and expression could discriminate ESCC from normal tissue. Five-year overall survival was shorter in underexpressed patients, and expression level was related to 5-year overall survival. and expression were independent prognosis indicators in ESCC patients. Our findings shed new light on the clinical significance of and in ESCC carcinogenesis.
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http://dx.doi.org/10.2217/bmm-2020-0432DOI Listing
October 2020

The abnormalities of coagulation and fibrinolysis in acute lung injury caused by gas explosion.

Kaohsiung J Med Sci 2020 Nov 9;36(11):929-936. Epub 2020 Jul 9.

Institute of Trauma and Orthopedics, Xinxiang Medical University, Xinxiang, China.

Acute lung injury (ALI) caused by gas explosion is common, and warrants research on the underlying mechanisms. Specifically, the role of abnormalities of coagulation and fibrinolysis in this process has not been defined. It was hypothesized that the abnormal coagulation and fibrinolysis promoted ALI caused by gas explosion. Based on the presence of ALI, 74 cases of gas explosion injury were divided into the ALI and non-ALI groups. The results of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and platelet count (PLT) were collected within 24 hours and compared between the groups. ALI models caused by gas explosion were established in Sprague Dawley rats, and injuries were evaluated using hematoxylin and eosin (HE) staining and histopathological scoring. Moreover, the bronchoalveolar lavage fluid (BALF) was collected to examine thrombin-antithrombin complex (TAT), tissue factor (TF), tissue factor pathway inhibitor (TFPI), and plasminogen activator inhibitor-1 (PAI-1) levels by enzyme-linked immunosorbent assay (ELISA). The patients in ALI group had shorter PT and longer APTT, raised concentration of FIB and decreased number of PLT, as compared to the non-ALI group. In ALI rats, the HE staining revealed red blood cells in alveoli and interstitial thickening within 2 hours which peaked at 72 hours. The levels of TAT/TF in the BALF increased continually until the seventh day, while the PAI-1 was raised after 24 hours and 7 days. The TFPI was elevated after 2 hours and 24 hours, and then decreased after 72 hours. Abnormalities in coagulation and fibrinolysis in lung tissues play a role in ALI caused by gas explosion.
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http://dx.doi.org/10.1002/kjm2.12262DOI Listing
November 2020

Prox1 induces new lymphatic vessel formation and promotes nerve reconstruction in a mouse model of sciatic nerve crush injury.

J Anat 2020 11 9;237(5):933-940. Epub 2020 Jun 9.

Department of Anatomy and Physiology, Shandong College of Traditional Chinese Medicine, Yantai, China.

The peripheral nervous system lacks lymphatic vessels and is protected by the blood-nerve barrier, which prevents lymphocytes and antibodies from entering the neural parenchyma. Peripheral nerve injury results in degeneration of the distal nerve and myelin degeneration causes macrophage aggregation, T lymphocyte infiltration, major histocompatibility complex class II antigen expression, and immunoglobulin G deposition in the nerve membrane, which together result in nerve edema and therefore affect nerve regeneration. In the present paper, we show myelin expression was absent from the sciatic nerve at 7 days after injury, and the expression levels of lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) and Prospero Homeobox 1 (Prox1) were significantly increased in the sciatic nerve at 7 days after injury. The lymphatic vessels were distributed around the myelin sheath and co-localized with lymphatic endothelial cells. Prox1 induces the formation of new lymphatic vessels, which play important roles in the elimination of tissue edema as well as in morphological and functional restoration of the damaged nerve. This study provides evidence of the involvement of new lymphatic vessels in nerve repair after sciatic nerve injury.
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http://dx.doi.org/10.1111/joa.13247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542192PMC
November 2020

Mediating K/H Transport on Organelle Membranes to Selectively Eradicate Cancer Stem Cells with a Small Molecule.

J Am Chem Soc 2020 06 4;142(24):10769-10779. Epub 2020 Jun 4.

Morningside Laboratory for Chemical Biology, Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China.

Molecules that are capable of disrupting cellular ion homeostasis offer unique opportunities to treat cancer. However, previously reported synthetic ion transporters showed limited value, as promiscuous ionic disruption caused toxicity to both healthy cells and cancer cells indiscriminately. Here we report a simple yet efficient synthetic K transporter that takes advantage of the endogenous subcellular pH gradient and membrane potential to site-selectively mediate K/H transport on the mitochondrial and lysosomal membranes in living cells. Consequent mitochondrial and lysosomal damages enhanced cytotoxicity to chemo-resistant ovarian cancer stem cells (CSCs) via apoptosis induction and autophagy suppression with remarkable selectivity (up to 47-fold). The eradication of CSCs blunted tumor formation in mice. We believe this strategy can be exploited in the structural design and applications of next-generation synthetic cation transporters for the treatment of cancer and other diseases related to dysfunctional K channels.
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http://dx.doi.org/10.1021/jacs.0c02134DOI Listing
June 2020

Long-term survival with targeted therapy in an advanced non-small cell lung cancer patient based on genetic profiling.

Transl Lung Cancer Res 2020 Apr;9(2):373-378

Department of Respiratory Medicine, Shanxi Provincial Cancer Hospital, Taiyuan 030001, China.

Non-small cell lung cancer (NSCLC) is a profoundly devastating disease that is the leading cause of cancer-related death worldwide. With the rapid development of next-generation sequencing (NGS), which has supplied the ability to decode tumors at the DNA level, so that targeted therapy plays a crucial role in improving NSCLC survival. We first reported a 32-year-old Chinese female patient received the ninth-line treatment, who was initially diagnosed with advanced NSCLC with 19 deletion. The patient had a satisfactory clinical response to initial gefitinib treatment. Subsequently, an T790M mutation was detected from plasma-derived circulating tumor DNA (ctDNA) by ddPCR after disease progression, while NGS did not. Osimertinib was still tried but had no therapeutic effect. Then the disease even progressed on the administration of chemotherapy and gefitinib in succession. Rebiopsy for NGS detection was performed, and gefitinib plus anlotinib/vemurafenib were tried. And then, gefitinib plus crizotinib were administrated for amplification after the third biopsy. Furthermore, chemotherapy combined with immunotherapy was performed due to the PD-L1 positive expression. Up to now, osimertinib treatment was undertaken to base on an exon 20 T790M mutation using NGS-based genotyping in cerebrospinal fluid (CSF) ctDNA. Tumor genome dynamic monitoring can identify tumor driving genes and drug resistance mechanisms to guide tumor treatment. This study found that the total survival time of advanced NSCLC patients was more than four years after chemoradiotherapy and targeted therapy, indicating the significance of dynamic monitoring of gene alterations for cancer treatment.
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http://dx.doi.org/10.21037/tlcr.2020.01.21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225131PMC
April 2020

Alkyl-Substituted Cucurbit[6]uril Bridged β-Cyclodextrin Dimer Mediated Intramolecular FRET Behavior.

J Org Chem 2020 May 13;85(9):6131-6136. Epub 2020 Apr 13.

College of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China.

A novel triazolyl bridged cucurbituril (CB)-cyclodextrin (CD) dimer was synthesized via click reaction of monopropargyl modified octamethylcucurbit[6]uril and mono-6-azido-β-cyclodextrin. Moreover, it could form stable supramolecular inclusion complexes possessing efficient fluorescence resonance energy transfer, which benefited from the fact that CD and CB can bind amantadine- and pyridinium-containing fluorophores simultaneously. The supramolecular inclusion complex behaviors were investigated by NMR spectroscopy, UV-vis absorption, and fluorescence spectroscopy.
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http://dx.doi.org/10.1021/acs.joc.9b03513DOI Listing
May 2020

piR-823 demonstrates tumor oncogenic activity in esophageal squamous cell carcinoma through DNA methylation induction via DNA methyltransferase 3B.

Pathol Res Pract 2020 Apr 5;216(4):152848. Epub 2020 Feb 5.

Anyang Key Laboratory for Esophageal Cancer Research, Anyang Cancer Hospital, the Forth Affiliated Hospital of Henan University of Science and Technology, Anyang, Henan, People's Republic of China. Electronic address:

Piwi-interacting RNAs (piRNAs) dysregulation occurs frequently in extensive cancers. However, there was no report about piRNA expression in esophageal cancer (EC). In this study, the expression levels of piR-823 and DNMT1, DNMT3A, DNMT3B were detected in 54 pairs of ESCC tissues and adjacent normal tissues using the quantitative real-time polymerase chain reaction method. Pearson's chi-squared test and receiver operating characteristic curves were established to evaluate the diagnostic and prognostic value of piR-823 in ESCC. Spearman's correlation analysis was used to evaluate the association between piR-823 and DNMTs. We found that piR-823 was significantly upregulated in ESCC tissues compared with matched normal tissues (P = 0.0213), the level of piR-823 was significantly associated with lymph node metastasis (P = 0.042). The ROC curve analysis of piR-823 expression level yielded an area under the ROC curve value of 0.713 (P = 0.0001). DNMT3B was upregulated in ESCC tissues compared with matched normal tissues (P = 0.0286). There was an obvious positive correlation between piR-823 and DNMT3B expression (r = 0.6420, P < 0.0001). In conclusion, for the first time, we provided evidence about piRNA expression in EC. piRNA-823 and DNMT3B were both upregulated in ESCC and positively correlated with each other, suggesting the tumor oncogenic role of piR-823 in ESCC to epigenetically induce aberrant DNA methylation through DNMT3B. In addition, piRNA-823 showed high specificity in detecting ESCC and higher piRNA-823 level indicated higher risk of lymph node metastasis, suggesting its diagnostic and prognostic biomarker potential.
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http://dx.doi.org/10.1016/j.prp.2020.152848DOI Listing
April 2020

Association between polymorphisms in the genes, and smoking, alcohol and upper digestive tract carcinomas in a high-incidence area of northern China.

Oncol Lett 2019 Aug 7;18(2):1267-1277. Epub 2019 Jun 7.

Anyang Key Laboratory for Esophageal Cancer Research, Anyang Cancer Hospital, Anyang, Henan 455000, P.R. China.

Metabolic gene variants, smoking, and alcohol consumption are important upper digestive tract cancer (UDTC) risk factors. However, the gene-gene and gene-environment interactions remain unclear. A case-control study in a high incidence area for upper digestive tract cancer was conducted in China. DNA was extracted from buffy coat samples for PCR or PCR-restriction fragment length polymorphism. Smoking and alcohol drinking status was determined by questionnaires. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the associations. After adjusting for confounding factors, smoking increased esophageal cancer (EC), gastric cardia cancer (GCC) and gastric antral carcinoma (GAC) risk by 3.594, 4.658, and 3.999-fold, respectively. Alcohol consumption increased EC, GCC and GAC risk by 1.953, 2.442 and 1.765-fold, respectively. The cytochrome P4501A1 ( rs4646903 T>C polymorphism increased GCC risk, the cytochrome P4502E1 ( rs2031920 C>T polymorphism increased EC risk, while the null genotype decreased EC risk. An association existed between the following: rs4646903 and smoking in EC, GCC and GAC; rs4646903 and alcohol consumption in EC and GCC; rs2031920 and smoking in EC, GCC and GAC and rs2031920 and alcohol consumption in EC and GCC. No association was observed between and . The glutathione S-transferase mu 1 () null genotype decreased EC risk (OR=0.510). Smoking/drinking are upper digestive tract cancer risk factors. The rs4646903 and rs2031920 polymorphisms were risk factors of GCC or EC, and the null genotype may serve a protective role against EC. The results of the present study indicated that gene-environment interactions increase the risk of UDTC.
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http://dx.doi.org/10.3892/ol.2019.10455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607096PMC
August 2019

Decreased expression of SPINT1-AS1 and SPINT1 mRNA might be independent unfavorable prognostic indicators in esophageal squamous cell carcinoma.

Onco Targets Ther 2019 20;12:4755-4763. Epub 2019 Jun 20.

The Key Laboratory for Tumor Translational Medicine, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, People's Republic of China.

The serine peptidase inhibitor, Kunitz type 1 antisense RNA1 (), a long non-coding RNA , has been linked to cancer progression. In this study, we aimed to explore the expression in matched esophageal squamous cell carcinoma (ESCC) and normal tissues, and analyze the potential correlations of expression with clinicopathological characteristics, in order to evaluate its prognosis and therapeutic value. SPINT1-AS1 expression was detected in 99 cases of matched ESCC and normal tissues samples using the quantitative real-time polymerase chain reaction method. The expression level (△Ct) of and was significantly downregulated in ESCC tissues compared with matched normal tissues (=0.0005; =0.0002, respectively), and there was an obvious positive correlation between and expression. Clinicopathological characteristics indicated that expression was correlated with age and tumor size, while SPINT1 mRNA expression was correlated with age and gender. The receiver operating characteristic (ROC) curve analysis of the expression level of and yielded an area under the ROC curve value of 0.638 and 0.625, respectively. The overall survival is shorter in patients with low expressed than those with high levels of (=0.044), and expression level is associated with the OS (=0.001). Univariate and multivariate analysis suggested that was an independent prognostic indicator in ESCC. We found that the expression of and is downregulated in ESCC tissues, which could contribute to tumor progression. and may be therapeutic targets and prognosis markers for ESCC.
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http://dx.doi.org/10.2147/OTT.S206448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591775PMC
June 2019

Recent Progress of Imprinted Polymer Photonic Waveguide Devices and Applications.

Polymers (Basel) 2018 May 31;10(6). Epub 2018 May 31.

School of Optoelectronic Engineering and Instrumentation Science, Dalian University of Technology, Dalian 116024, China.

Polymers are promising materials for fabricating photonic integrated waveguide devices. Versatile functional devices can be manufactured using a simple process, with low cost and potential mass-manufacturing. This paper reviews the recent progress of polymer photonic integrated devices fabricated using the UV imprinting technique. The passive polymer waveguide devices for wavelength filtering, power splitting, and light collecting, and the active polymer waveguide devices based on the thermal-optic tuning effect, are introduced. Then, the electro-optic (EO) modulators, by virtue of the high EO coefficient of polymers, are described. Finally, the photonic biosensors, which are based on low-cost and biocompatible polymer platforms, are presented.
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http://dx.doi.org/10.3390/polym10060603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404155PMC
May 2018

High expression of HLA-DQA1 predicts poor outcome in patients with esophageal squamous cell carcinoma in Northern China.

Medicine (Baltimore) 2019 Feb;98(8):e14454

The Key Laboratory for Tumor Translational Medicine, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang.

Background: Our previous studies demonstrate that the major histocompatibility complex (MHC) is associated with the progression of esophageal squamous cell carcinoma (ESCC). HLA-DQA1, which belongs to the MHC Class II family, may be a potential biomarker in ESCC progression. However, the association between HLA-DQA1 and ESCC in high-incidence area of northern China has not been well characterized. The purpose of this study is to investigate the relationship of HLA-DQA1 expression with the progression and prognosis of ESCC.

Methods: We analyzed the expression profiles of HLA-DQA1 in esophageal cancer (EC) samples in the TCGA database and validated HLA-DQA1 expression by immunohistochemistry, western blotting, and quantitative reverse-transcription polymerase chain reaction in matched EC and normal tissues, respectively. The correlation between HLA-DQA1 expression and clinicopathologic characteristics of ESCC was further analyzed.

Result: Immunohistochemical analysis indicated that the expression level of HLA-DQA1 in ESCC tissues was significantly higher than the matched normal tissues (P < .001). HLA-DQA1 mRNA and protein expression were significantly higher in ESCC tissues compared to the matched normal tissues. Patients with family history negative or with tumor sizes >4 cm were associated with higher HLA-DQA1 expression levels. A prognostic significance of HLA-DQA1 was also found by the Log-rank method, in which high expression of HLA-DQA1 was correlated with a shorter overall survival time. The receiver operating characteristic (ROC) curve analysis yielded the area under the ROC curve value of 0.693. Univariate and multivariate analyses also suggest that high expression of HLA-DQA1 is a potential indicator for poor prognosis of ESCC.

Conclusions: Our results demonstrate that HLA-DQA1 plays an important role in ESCC progression and may be a biomarker for ESCC diagnosis and prognosis, as well as a potential target for the treatment of patients with ESCC.
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http://dx.doi.org/10.1097/MD.0000000000014454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408075PMC
February 2019

A New Member of the Inverted Cucurbit[n]uril Family.

Chemistry 2017 Dec 6;23(67):16953-16956. Epub 2017 Nov 6.

Key Laboratory of Macrocyclic and Supramolecular Chemistry of Guizhou Province, Guizhou University, Guiyang, 550025, P.R. China.

A new inverted cucurbituril, namely inverted hexamethylcucurbit[3,3]uril (iMe Q[3,3]), has been isolated and characterized. It incorporates a single inverted un-substituted glycoluril unit oriented towards the interior of the cavity, shows good solubility in water and organic solvents (DMSO), and exhibits different selectivity for guests to those of iQ[6] and other known Q[6]s.
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http://dx.doi.org/10.1002/chem.201704069DOI Listing
December 2017

Novel genetic locus at MHC region for esophageal squamous cell carcinoma in Chinese populations.

PLoS One 2017 11;12(5):e0177494. Epub 2017 May 11.

Henan Key Laboratory for Esophageal Cancer Research, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Background: Our previous genome-wide association study (GWAS) identified three independent single nucleotide polymorphisms (SNPs) in human major histocompatibility complex (MHC) region showing association with esophageal squamous cell carcinoma (ESCC). In this study, we increased GWAS sample size on MHC region and performed validation in an independent ESCC cases and normal controls with aim to find additional loci at MHC region showing association with an increased risk to ESCC.

Methods: The 1,077 ESCC cases and 1,733 controls were genotyped using Illumina Human 610-Quad Bead Chip, and 451 cases and 374 controls were genotyped using Illumina Human 660W-Quad Bead Chip. After quality control, the selected SNPs were replicated by TaqMan genotyping assay on another 2,026 ESCC cases and 2,384 normal controls.

Results: By excluding low quality SNPs in primary GWAS screening, we selected 2,533 SNPs in MHC region for association analysis, and identified 5 SNPs with p <10-4. Further validation analysis in an independent case-control cohort confirmed one of the 5 SNPs (rs911178) that showed significant association with ESCC. rs911178 (PGWAS = 6.125E-04, OR = 0.644 and Preplication = 1.406E-22, OR = 0.489) was located at upstream of SCAND3.

Conclusion: The rs911178 (SCAND3 gene) in MHC region is significantly associated with high risk of ESCC. This study not only reveal the potential role of MHC region for the pathogenesis of ESCC, but also provides important clues for the establishment of tools and methods for screening high risk population of ESCC.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0177494PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426749PMC
September 2017

Mono- and Dihydroxylated Symmetrical Octamethylcucurbiturils and Allylated Derivatives.

Org Lett 2016 11 21;18(21):5544-5547. Epub 2016 Oct 21.

Key Laboratory of Macrocyclic and Supramolecular Chemistry of Guizhou Province, Guizhou University , Guiyang, Guizhou 550025, China.

Mono- and dihydroxylated symmetrical octamethylcucurbit[6]urils {(OH)OMeQ[6] and (OH)OMeQ[6]} were prepared using a photochemical method to introduce limited alcohol group(s) directly to the parent symmetrical octamethylcucurbit[6]uril (OMeQ[6]), and the resulting compounds were verified by H NMR, Xevo Q-TOF MS, and X-ray crystallography. Further chemical modification of mono- and dihydroxylated OMeQ[6] was also performed.
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http://dx.doi.org/10.1021/acs.orglett.6b02789DOI Listing
November 2016

A small synthetic molecule functions as a chloride-bicarbonate dual-transporter and induces chloride secretion in cells.

Chem Commun (Camb) 2016 May;52(46):7380-3

Morningside Laboratory for Chemical Biology, Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China.

A C2 symmetric small molecule composed of l-phenylalanine and isophthalamide was found to function as a Cl(-)/HCO3(-) dual transporter and self-assemble into chloride channels. In Ussing-chamber based short-circuit current measurements, this molecule elicited chloride-dependent short-circuit current (Isc) increase in both Calu-3 cell and CFBE41o-cell (with F508del mutant CFTR) monolayers.
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http://dx.doi.org/10.1039/c6cc01964aDOI Listing
May 2016

Traditional chinese medicine tongxinluo improves cardiac function of rats with dilated cardiomyopathy.

Evid Based Complement Alternat Med 2014 28;2014:323870. Epub 2014 Dec 28.

Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.

The study aimed at testing the hypothesis that tongxinluo capsule might exert its cardioprotective effect by preventing ventricular remodeling and improving coronary microvascular function in a rat model of doxorubicin-induced dilated cardiomyopathy (DCM). Rats that survived DCM induction were randomly divided into three groups to be given 1.5 g·kg(-1)·day(-1) (TXL-H, n = 9) or 0.15 g·kg(-1)·day(-1) (TXL-L, n = 10) of tongxinluo, or normal saline at the same volume (DCM-C, n = 10) intragastrically. Age matched normal rats treated with normal saline were used as normal controls (NOR-C, n = 9). After four weeks of treatment, the DCM-C, TXL-H, and TXL-L groups exhibited significant cardiac dysfunction, left ventricular remodeling, and coronary microvascular dysfunction, compared with the NOR-C rats. However, myocardial functional parameters were significantly improved and microvascular density (MVD) increased in the TXL-H group compared with the DCM-C group (all P < 0.01). Left ventricular remodeling was prevented. There were close linear relationships between CVF and LVEF (r = -0.683, P < 0.05), MVD and LVEF (r = 0.895, P < 0.05), and MVD and CVF (r = -0.798, P < 0.05). It was indicated that high-dose tongxinluo effectively improved cardiac function in rat model of DCM.
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http://dx.doi.org/10.1155/2014/323870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295346PMC
January 2015

Variations in the MHC region confer risk to esophageal squamous cell carcinoma on the subjects from high-incidence area in northern China.

PLoS One 2014 4;9(3):e90438. Epub 2014 Mar 4.

Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China.

Background: The human major histocompatibility complex (MHC) is the most important region in vertebrate genome, and is crucial in innate immunity. Recent studies have demonstrated the possible role of polymorphisms in the MHC region to high risk for esophageal squamous cell carcinoma (ESCC). Our previous genome-wide association study (GWAS) has indicated that the MHC region may confer important risk loci for ESCC, but without further fine mapping. The aim of this study is to further identify the risk loci in the MHC region for ESCC in Chinese population.

Methods: Conditional logistic regression analysis (CLRA) was performed on 24 single nucleotide polymorphisms (SNPs) within the MHC region, which were obtained from the genetically matched 937 cases and 692 controls of Chinese Han population. The identified promising SNPs were further correlated with clinical and clinicopathology characteristics. Immunohistochemistry was performed to explore the protein expression pattern of the related genes in ESCC and neighboring normal tissues.

Results: Of the 24 promising SNPs analyzed, we identified three independent SNPs in the MHC region associated with ESCC: rs35399661 (P = 6.07E-06, OR = 1.71, 95%CI = 1.36-2.17), rs3763338 (P = 1.62E-05, OR = 0.63, 95%CI = 0.50-0.78) and rs2844695 (P = 7.60E-05, OR = 0.74, 95%CI = 0.64-0.86). These three SNPs were located at the genes of HLA-DQA1, TRIM27, and DPCR1, respectively. Further analyses showed that rs2844695 was preferentially associated with younger ESCC cases (P = 0.009). The positive immunostaining rates both for HLA-DQA1 and TRIM27 were much higher in ESCC tissues than in neighboring normal tissues (69.4% vs. 26.8% for HLA-DQA1 and 77.6% vs. 47.8% for TRIM27, P<0.001). Furthermore, the overexpression of HLA-DQA1 is correlated significantly with age (P = 0.001) and family history (P<0.001).

Conclusion: This study for the first time provides evidence that multiple genetic factors within the MHC region confer risk to ESCC on the subjects from high-risk area in northern China.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0090438PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942432PMC
February 2015

Catalytic asymmetric 1,2-addition of α-isothiocyanato phosphonates: synthesis of chiral β-hydroxy- or β-amino-substituted α-amino phosphonic acid derivatives.

Angew Chem Int Ed Engl 2014 Feb 13;53(7):1862-6. Epub 2014 Jan 13.

Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000 (China).

α-Amino phosphonic acid derivatives are considered to be the most important structural analogues of α-amino acids and have a very wide range of applications. However, approaches for the catalytic asymmetric synthesis of such useful compounds are very limited. In this work, simple, efficient, and versatile organocatalytic asymmetric 1,2-addition reactions of α-isothiocyanato phosphonate were developed. Through these processes, derivatives of β-hydroxy-α-amino phosphonic acid and α,β-diamino phosphonic acid, as well as highly functionalized phosphonate-substituted spirooxindole, can be efficiently constructed (up to 99 % yield, d.r. >20:1, and >99 % ee). This novel method provides a new route for the enantioselective functionalization of α-phosphonic acid derivatives.
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http://dx.doi.org/10.1002/anie.201308514DOI Listing
February 2014

Association between CYP1A1 polymorphisms and esophageal cancer: a meta-analysis.

Mol Biol Rep 2013 Oct 25;40(10):6035-42. Epub 2013 Sep 25.

The Key Laboratory for Tumor Translational Medicine, The Third Affiliated Hospital, Xinxiang Medical University, Xinxiang, Henan, China.

Cytochrome P4501A1 (CYP1A1) enzyme is a member of the CYP superfamily of enzymes. CYP1A1 A2455G and T3801C are two most commonly studied polymorphisms loci. Previous studies have reported that CYP1A1 polymorphisms increase esophageal cancer (EC) risk. However, the results remain controversial and ambiguous. To further investigate the association between CYP1A1 polymorphisms (A2455G and T3801C) and EC risk. A meta-analysis was performed to investigate the association between CYP1A1 polymorphisms and EC risk. A total of 13 articles (A2455G and T3801C: 2 papers, A2455G: 8 papers, T3801C: 3 papers) from the PubMed containing information on the CYP1A1 polymorphisms and EC were included in this meta-analysis, with summational sample size of 1,881 EC cases and 3,786 controls. Stratified analysis was performed to evaluate the ethnicity (Caucasians and Asian) and histopathology type (esophageal squamous cell carcinoma and esophageal adenocarcinoma) effect. No obvious publication bias in the two polymorphisms was observed. Our meta-analysis revealed a significant association between the A2455G polymorphism and EC (OR = 1.55 per A allele, 95 % CI 1.29-1.85, P < 0.001). Stratification analysis by ethnicity and histopathology type showed significant association in the population of Asian origin (OR = 1.55, 95 % CI 1.28-1.89, P < 0.001) and in histopathology type of ESCC (OR = 1.40, 95 % CI 1.19-1.65, P < 0.001). We didn't observe the significant association between CYP1A1 T3801C polymorphism and EC. We observed a difference of allele frequencies between Caucasian and Asian population in the meta-analysis. The allele frequencies in our meta-analysis were consistent with the allele frequencies in 1000 Genome Project. Our meta-analysis demonstrated distinct evidence that CYP1A1 A2455G polymorphism was associated with the risk of EC.
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http://dx.doi.org/10.1007/s11033-013-2713-1DOI Listing
October 2013

Catalytic enantioselective ring-opening reaction of meso-aziridines with α-isothiocyanato imides.

Chemistry 2013 Jul 7;19(29):9476-80. Epub 2013 Jun 7.

Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Biochemistry and Molecular Biology, School of Life Science, Lanzhou University, Lanzhou 730000, P. R. China.

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http://dx.doi.org/10.1002/chem.201300297DOI Listing
July 2013

Catalytic asymmetric Michael addition/cyclization of isothiocyanato oxindoles: highly efficient and versatile approach for the synthesis of 3,2'-pyrrolidinyl mono- and bi-spirooxindole frameworks.

Chemistry 2013 Jan 18;19(4):1184-8. Epub 2012 Dec 18.

Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Biochemistry and Molecular Biology, School of Life Science, Lanzhou University, Lanzhou 730000, PR China.

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http://dx.doi.org/10.1002/chem.201204114DOI Listing
January 2013

Novel GATA4 mutations in lone atrial fibrillation.

Int J Mol Med 2011 Dec 26;28(6):1025-32. Epub 2011 Aug 26.

Department of Emergency, Shanghai Chest Hospital, Medical College of Shanghai Jiaotong University, Shanghai 200030, PR China.

Atrial fibrillation (AF) is the most frequent cardiac arrhythmia and is a major cause of morbidity and mortality. Previous studies have established genetic defects as a risk factor for AF in a minority of patients. However, AF is of substantial genetic heterogeneity and the molecular determinants for AF in a majority of cases remain unclear. In this study, the entire coding sequence and splice junctions of GATA4, which encodes a zinc-finger transcription factor essential for cardiogenesis, were sequenced in 160 unrelated patients with lone AF. A total of 200 unrelated ethnically matched healthy individuals were used as controls. The available relatives of the patient carrying an identified mutation were genotyped. The functional characteristics of the mutant GATA4 were analyzed using a luciferase reporter assay system. As a result, two novel heterozygous GATA4 mutations of p.G16C and p.H28D, were identified in 2 unrelated families with AF, respectively, which co-segregated with AF in each family with complete penetrance. Functional analysis demonstrated that the mutations of GATA4 were associated with a significantly decreased transcriptional activity. The findings expand the mutation spectrum of GATA4 linked to AF and provide novel insight into the molecular mechanism involved in the pathogenesis of AF.
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http://dx.doi.org/10.3892/ijmm.2011.783DOI Listing
December 2011

Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies susceptibility loci at PLCE1 and C20orf54.

Nat Genet 2010 Sep 22;42(9):759-63. Epub 2010 Aug 22.

Cancer Research Center, Xinxiang Medical University, Xinxiang, Henan, China.

We performed a genome-wide association study of esophageal squamous cell carcinoma (ESCC) by genotyping 1,077 individuals with ESCC and 1,733 control subjects of Chinese Han descent. We selected 18 promising SNPs for replication in an additional 7,673 cases of ESCC and 11,013 control subjects of Chinese Han descent and 303 cases of ESCC and 537 control subjects of Chinese Uygur-Kazakh descent. We identified two previously unknown susceptibility loci for ESCC: PLCE1 at 10q23 (P(Han combined for ESCC) = 7.46 x 10(-56), odds ratio (OR) = 1.43; P(Uygur-Kazakh for ESCC) = 5.70 x 10(-4), OR = 1.53) and C20orf54 at 20p13 (P(Han combined for ESCC) = 1.21 x 10(-11), OR = 0.86; P(Uygur-Kazakh for ESCC) = 7.88 x 10(-3), OR = 0.66). We also confirmed association in 2,766 cases of gastric cardia adenocarcinoma cases and the same 11,013 control subjects (PLCE1, P(Han for GCA) = 1.74 x 10(-39), OR = 1.55 and C20orf54, P(Han for GCA) = 3.02 x 10(-3), OR = 0.91). PLCE1 and C20orf54 have important biological implications for both ESCC and GCA. PLCE1 might regulate cell growth, differentiation, apoptosis and angiogenesis. C20orf54 is responsible for transporting riboflavin, and deficiency of riboflavin has been documented as a risk factor for ESCC and GCA.
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http://dx.doi.org/10.1038/ng.648DOI Listing
September 2010

Studies of lysozyme binding to histamine as a ligand for hydrophobic charge induction chromatography.

Biotechnol Prog 2010 Jan-Feb;26(1):134-41

Dept. of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, P.R. China.

Histamine was immobilized on Sepharose CL-6B (Sepharose) for use as a ligand of hydrophobic charge induction chromatography (HCIC) of proteins. Lysozyme adsorption onto Histamine-Sepharose (HA-S) was studied by adsorption equilibrium and calorimetry to uncover the thermodynamic mechanism of the protein binding. In both the experiments, the influence of salt (ammonium sulfate and sodium sulfate) was examined. Adsorption isotherms showed that HA-S exhibited a high salt tolerance in lysozyme adsorption. This property was well explained by the combined contributions of hydrophobic interaction and aromatic stacking. The isotherms were well fitted to the Langmuir equation, and the equilibrium parameters for lysozyme adsorption were obtained. In addition, thermodynamic parameters (DeltaH(ads), DeltaS(ads), and DeltaG(ads)) for the adsorption were obtained by isothermal titration calorimetry by titrating lysozyme solutions into the adsorbent suspension. Furthermore, free histamine was titrated into lysozyme solution in the same salt-buffers. Compared with the binding of lysozyme to free histamine, lysozyme adsorption onto HA-S was characterized by a less favorable DeltaG(ads) and an unfavorable DeltaS(ads) because histamine was covalently attached to Sepharose via a three-carbon-chain spacer. Consequently, the immobilized histamine could only associate with the residues on the protein surface rather than those in the hydrophobic pocket, causing a less favorable orientation between histamine and lysozyme. Further comparison of thermodynamic parameters indicated that the unfavorable DeltaS(ads) was offset by a favorable DeltaH(ads), thus exhibiting typical enthalpy-entropy compensation. Moreover, thermodynamic analyses indicated the importance of the dehydration of lysozyme molecule and HA-S during the adsorption and a substantial conformational change of the protein during adsorption. The results have provided clear insights into the adsorption mechanisms of lysozyme onto the new HCIC material.
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http://dx.doi.org/10.1002/btpr.295DOI Listing
May 2010

[Effects of different interference orders of acupuncture and exercise therapy on the amplitude of somatosensory evoked potential (SEP) in the patient of hemiplegia after stroke].

Zhongguo Zhen Jiu 2006 Dec;26(12):869-72

Department of TCM, Fuzhou General Hospital, Nanjing Military Area, Fujian 350025, China.

Objective: To observe effects of different interference orders of acupuncture and exercise therapy on the therapeutic effect.

Methods: The patients of hemiplegia after stroke in the stage of recovery were randomly divided into two groups: raising handclasp of Bobath after electroacupuncture at Quchi (LI 11) and Hegu (LI 4) on the affected side or electroacupuncture at Quchi (LI 11) and Hegu (LI 4) on the affected side after raising handclasp of Bobath. The changes of SEP on the affected side were recorded and compared.

Results: SEP on the affected side significantly increased in the patients after treatment of simple electroacupuncture or exercise therapy (P < 0.01), with no significant difference between the two groups (P > 0.05). There was a very significant difference in SEP on the affected side between the group of exercise treatment after electroacupuncture and the group of electroacupuncture after exercise therapy (P < 0.01).

Conclusion: Both electroacupuncture and exercise therapy can immediately improve SEP of the patient in the recovery stage, and the groups of the different interference orders of electroacupuncture and exercise have different effects on SEP, and raising handclasp of Bobath after electroacupuncture is better for improvement in cerebral function of the patient.
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December 2006