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| 1 | NKX6.3 protects against gastric mucosal atrophy by downregulatingβ-amyloid production显示文摘BACKGROUND Atrophic gastritis is characterized by loss of appropriate glands and reduction in gastric secretory function due to chronic inflammatory processes in gastric mucosa. Moreover, atrophic gastritis is considered as a precancerous condition of gastric cancer. However, little is known about the molecular mechanism underlying gastric mucosal atrophy and its contribution to gastric carcinogenesis.Thus, we hypothesized that transcription factor NKX6.3 might be involved in maintaining gastric epithelial homeostasis by regulating amyloid β(Aβ)production.AIM To determine whether NKX6.3 might protect against gastric mucosal atrophy by regulating Aβ production.METHODS We identified NKX6.3 depletion induced cell death by cell count and Western blot assay. Production and mechanism of Aβ oligomer were analyzed by enzymelinked immunosorbent assay, Western blot, immunoprecipitation, real-timequantitative polymerase chain reaction and immunofluorescence analysis. We further validated the correlation between expression of NKX6.3, Helicobacter pylori CagA, Aβ oligomer, apolipoprotein E(ApoE), and β-secretase 1(Bace1) in 55 gastric mucosae.RESULTS NKX6.3 depletion increased both adherent and floating cell populations in HFE-145 cells. Expression levels of cleaved caspase-3,-9, and poly ADP ribose polymerase were elevated in floating HFE-145^(shNKX6.3) cells. NKX6.3 depletion produced Aβ peptide oligomers, and increased expression of ApoE, amyloid precursor protein, Aβ, Bace1, low-density lipoprotein receptor, nicastrin, high mobility group box1, and receptor for advanced glycosylation end product proteins. In immunoprecipitation assay, γ-secretase complex was stably formed only in HFE-145^(shNKX6.3) cells. In gastric mucosae with atrophy, expression of Aβpeptide oligomer, ApoE, and Bace1 was detected and inversely correlated with NKX6.3 expression. Treatment with recombinant Aβ 1-42 produced Aβoligomeric forms and decreased cell viability in HFE-145^(shNKX6.3) cells. Additionally,NKX6.3 depletion increased expression of inflammatory cytokines and cyclooxygenase-2.CONCLUSION NKX6.3 inhibits gastric mucosal atrophy by regulating Aβ accumulation and inflammatory reaction in gastric epithelial cells. | Jung Hwan Yoon Yeon Soo Lee Olga Kim Hassan Ashktorab Duane T Smoot Suk Woo Nam Won Sang Park | 2019 | World Journal of Gastroenterology2019，25，3： | 6 |
| 2 | Histone deacetylase inhibitor pre-treatment enhances the efficacy of DNA-interacting chemotherapeutic drugs in gastric cancer显示文摘BACKGROUND The prognosis of gastric cancer continues to remain poor,and epigenetic drugs like histone deacetylase inhibitors(HDACi)have been envisaged as potential therapeutic agents.Nevertheless,clinical trials are facing issues with toxicity and efficacy against solid tumors,which may be partly due to the lack of patient stratification for effective treatments.To study the need of patient stratification before HDACi treatment,and the efficacy of pre-treatment of HDACi as a chemotherapeutic drug sensitizer.METHODS The expression activity of class 1 HDACs and histone acetylation was examined in human gastric cancer cells and tissues.The potential combinatorial regime of HDACi and chemotherapy drugs was defined on the basis of observed drug binding assays,chromatin remodeling and cell death.RESULTS In the present study,the data suggest that the differential increase in HDAC activity and the expression of class 1 HDACs are associated with hypoacetylation of histone proteins in tumors compared to normal adjacent mucosa tissue samples of gastric cancer.The data highlights for the first time that pretreatment of HDACi results in an increased amount of DNA-bound drugs associated with enhanced histone acetylation,chromatin relaxation and cell cycle arrest.Fraction-affected plots and combination index-based analysis show that pre-HDACi chemo drug combinatorial regimes,including valproic acid with cisplatin or oxaliplatin and trichostatin A with epirubicin,exhibit synergism with maximum cytotoxic potential due to higher cell death at low combined doses in gastric cancer cell lines.CONCLUSION Expression or activity of class 1 HDACs among gastric cancer patients present an effective approach for patient stratification.Furthermore,HDACi therapy in pretreatment regimes is more effective with chemotherapy drugs,and may aid in predicting individual patient prognosis. | Ramchandra Vigay Amnekar Shafqat Ali Khan Mudasir Rashid Bharat Khade Rahul Thorat Poonam Gera Shailesh V Shrikhande Duane T Smoot Hassan Ashktorab Sanjay Gupta | 2020 | World Journal of Gastroenterology2020，26，6： | 3 |
| 3 | Epicardium-to-fat transition in injured heart显示文摘 | Qiaozhen Liu Xiuzhen Huang Jin-Hee Oh Ruei-Zeng Lin Shengzhong Duan Ying Yu Rui Yang Ju Qiu Juan M Melero-Martin William T Pu Bin Zhou | 2014 | Cell Research2014，24，11： | 2 |
| 4 | Doping and electrical transport in silicon nanowires显示文摘 | Cui Y Duan X F Hu J T | 2000 | J Phys Chem B2000，104，22： | 2 |
| 5 | Effects of insulin-like growth factor-I and insulin in the in vitro uptake of sulfate by eel branchial cartilage : evidence for the presence of independent hepatic and pancreatic sulfation factors 显示文摘 | Duan C Hirano T | 1992 | J Endocrinol1992，133，： | 1 |
| 6 | Triterpene caffeoyl esters and diterpenes from Celastrus stephanotifolius 显示文摘 | Chen B Duan H Q Yoshihisa T | 1999 | Phytochemistry1999，51，5： | 1 |
| 7 | Structure,developmental expression,and physiological regulation of zebra fish IGF-binding protein-1显示文摘 | Maures T J Duan C | 2002 | Endocrinology2002，143，： | 1 |
| 8 | Fast speciation of mercury in seawater by short-column high-performance liquid chromatography hyphenated to inductively coupled plasma spectrometry after on-line cation exchange column preconcentration 显示文摘 | Jia X Y Gong D R Han Y Wei C Duan T C Chen H T | 2012 | Talanta2012，88，： | 1 |
| 9 | 查看详情显示文摘 | Duan B X Yang Y T | | 0，，： | 1 |
| 10 | Re- suits of bituminous coal gasification upon exposure to a pressurized pilot-plant circulating fluidized-bed (CFB) reac- tor 显示文摘 | DUAN Feng JIN t ao-sheng HUANG Ya-ji | 2010 | Energy and Fuels2010，24，5： | 1 |
| 11 | Reamed intramedullary nailingversus undreamed intramedullary nailing for shaft fracture of fe-mur: a systematic literature review 显示文摘 | Duan X Li T Mohammed AQ | 2011 | Arch Orlhop Trauma Surg2011，131，： | 1 |
| 12 | Building an Automatic Vehicle License-Plate Recognition System 显示文摘 | DUAN T D DU T L H PHUOC T V | 2005 | Int Conf Comput Sci2005，32，5： | 1 |
| 13 | Three dimensional thermal mechanical coupled simulation during hot rolling of aluminium alloy 300a 显示文摘 | Duan X Sheppard T | 2002 | Int J Mech Sci2002，44，10： | 1 |
| 14 | Evaluation of a sequential extraction for the speciation of Thorium in soils from Baotou area, Inner Mongolia 显示文摘 | GUO P R DUAN T C SONG X J | 2007 | Talanta2007，71，2： | 1 |
| 15 | Source identification of airborne Escherichia coli of swine house surroundings using ERIC-PCR and REP-PCR 显示文摘 | Duan H Chai T Liu J | 2009 | Environ Res2009，109，： | 1 |
| 16 | Hyperhomocysteinemia impairs angiogenesis in response to hindlimb ischemia显示文摘 | Duan J Murohara T Ikeda H | 2000 | Arterioscler Thromb Vasc Biol2000，20，12： | 1 |
| 17 | Plasma kinetics of growth hormone in the Japanese eel, Anguilla japonica 显示文摘 | Duan C Hirano T | 1991 | Aquaculture1991，95，12： | 1 |
| 18 | Determination of the optimal energy level in spectral CT imaging for displaying abdominal vessels in pediatric patients显示文摘 | Hu D Yu T Duan X | 2014 | Eur J Radiol2014，83，3： | 1 |
| 19 | Primary thrombocytopenic purpura and acquired hemolytic anemia:evidence for common etiology显示文摘 | EVANS R S TAKAHASHI K DUANE R T | 1951 | Arch Intern Med1951，87，： | 1 |
| 20 | 显示文摘 | Murohara T Ikeda H Duan J | 2000 | J Clin Invest2000，105，： | 1 |
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